The endocrinology of food intake

Abstract

Many questions must be considered with regard to consuming food, including when to eat, what to eat and how much to eat. Although eating is often thought to be a homeostatic behaviour, little evidence exists to suggest that eating is an automatic response to an acute shortage of energy. Instead, food intake can be considered as an integrated response over a prolonged period of time that maintains the levels of energy stored in adipocytes. When we eat is generally determined by habit, convenience or opportunity rather than need, and meals are preceded by a neurally-controlled coordinated secretion of numerous hormones that prime the digestive system for the anticipated caloric load. How much we eat is determined by satiation hormones that are secreted in response to ingested nutrients, and these signals are in turn modified by adiposity hormones that indicate the fat content of the body. In addition, many nonhomeostatic factors, including stress, learning, palatability and social influences, interact with other controllers of food intake. If a choice of food is available, what we eat is based on pleasure and past experience. This article reviews the hormones that mediate and influence these processes.

Key Points

  • Endocrine influences over eating are complex and include factors related to the body's energy needs (homeostatic factors) and to experience, habits and opportunity (nonhomeostatic factors)

  • Meal-anticipatory endocrine responses that are initiated by food cues before eating start the digestive process and reduce the incidence of meal-associated hyperglycaemia and other metabolic challenges

  • Although satiation hormones such as cholecystokinin and glucagon-like peptide 1 (GLP-1) determine how much a person eats, they have not proven efficacious as clinical treatments for reducing body weight

  • Adiposity hormones, such as leptin and insulin, change the sensitivity of the brain to satiation signals, thereby helping maintain stable levels of body fat and body weight over time

  • Stress, reproductive regulatory hormones and cardiovascular regulatory hormones interact with adiposity signals in complex ways to influence food intake

  • Although chronically altered levels of GLP-1, ghrelin and other gastrointestinal hormones are thought to underlie metabolic improvements following bariatric surgery, supporting evidence is lacking

Access options

Rent or Buy article

Get time limited or full article access on ReadCube.

from$8.99

All prices are NET prices.

Figure 1: Meal-fed rats that habitually receive food at time 0 begin making anticipatory responses >1 h before the anticipated meal.
Figure 2: Homeostatic controls determine meal size and are based on satiation signals such as cholecystokinin and glucagon-like peptide-1, adiposity signals such as leptin and insulin, and local nutrient levels reaching the ARC and other hypothalamic areas from the blood, including glucose and some fatty acids and amino acids.
Figure 3: Hormonal signals arising in the periphery influence areas of the brain involved in food intake in many ways.

References

  1. 1

    Woods, S. C. The control of food intake: behavioral versus molecular perspectives. Cell Metab. 9, 489–498 (2009).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  2. 2

    Stanley, S., Wynne, K., McGowan, B. & Bloom, S. Hormonal regulation of food intake. Physiol. Rev. 85, 1131–1158 (2005).

    Article  CAS  Google Scholar 

  3. 3

    Woods, S. C. & Ramsay, D. S. Food intake, metabolism and homeostasis. Physiol. Behav. 104, 4–7 (2011).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  4. 4

    Day, F. R. & Loos, R. J. Developments in obesity genetics in the era of genome-wide association studies. J. Nutrigenet. Nutrigenomics 4, 222–238 (2011).

    Article  Google Scholar 

  5. 5

    Fall, T. & Ingelsson, E. Genome-wide association studies of obesity and metabolic syndrome. Mol. Cell. Endocrinol. http://dx.doi.org/10.1016/j.mce.2012.08.018.

  6. 6

    Sandholt, C. H., Hansen, T. & Pedersen, O. Beyond the fourth wave of genome-wide obesity association studies. Nutr. Diabetes 2, e37 (2012).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  7. 7

    Yeo, G. S. & Heisler, L. K. Unraveling the brain regulation of appetite: lessons from genetics. Nat. Neurosci. 15, 1343–1349 (2012).

    Article  CAS  Google Scholar 

  8. 8

    Rucker, D., Padwal, R., Li, S. K., Curioni, C. & Lau, D. C. Long term pharmacotherapy for obesity and overweight: updated meta-analysis. BMJ 335, 1194–1199 (2007).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  9. 9

    Bradley, D., Magkos, F. & Klein, S. Effects of bariatric surgery on glucose homeostasis and type 2 diabetes. Gastroenterology 143, 897–912 (2012).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. 10

    Wing, R. R. & Phelan, S. Long-term weight loss maintenance. Am. J. Clin. Nutr. 82, 222S–225S (2005).

    Article  CAS  Google Scholar 

  11. 11

    Woods, S. C., Decke, E. & Vasselli, J. R. Metabolic hormones and regulation of body weight. Psychol. Rev. 81, 26–43 (1974).

    Article  CAS  Google Scholar 

  12. 12

    Pavlov, I. P. Conditioned Reflexes: An Investigation of the Physiological Activity of the Cerebral Cortex (Ed. Anrep, G. V.) (Oxford University Press, Humphrey Milford, 1927).

    Google Scholar 

  13. 13

    Teff, K. L. How neural mediation of anticipatory and compensatory insulin release helps us tolerate food. Physiol. Behav. 103, 44–50 (2011).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  14. 14

    Woods, S. C. The eating paradox: how we tolerate food. Psychol. Rev. 98, 488–505 (1991).

    Article  CAS  Google Scholar 

  15. 15

    Ahren, B. & Holst, J. J. The cephalic insulin response to meal ingestion in humans is dependent on both cholinergic and noncholinergic mechanisms and is important for postprandial glycemia. Diabetes 50, 1030–1038 (2001).

    Article  CAS  Google Scholar 

  16. 16

    Powley, T. L. The ventromedial hypothalamic syndrome, satiety, and a cephalic phase hypothesis. Psychol. Rev. 84, 89–126 (1977).

    Article  CAS  Google Scholar 

  17. 17

    Power, M. L. & Schulkin, J. Anticipatory physiological regulation in feeding biology: cephalic phase responses. Appetite 50, 194–206 (2008).

    Article  Google Scholar 

  18. 18

    Woods, S. C. Conditioned hypoglycemia: effect of vagotomy and pharmacological blockade. Am. J. Physiol. 223, 1424–1427 (1972).

    Article  CAS  Google Scholar 

  19. 19

    Berthoud, H. R., Bereiter, D. A., Trimble, E. R., Siegel, E. G. & Jeanrenaud, B. Cephalic phase, reflex insulin secretion. Neuroanatomical and physiological characterization. Diabetologia 20 (Suppl.), 393–401 (1981).

    Article  CAS  Google Scholar 

  20. 20

    Teff, K. L., Mattes, R. D. & Engelman, K. Cephalic phase insulin release in normal weight males: verification and reliability. Am. J. Physiol. 261, E430–E436 (1991).

    CAS  PubMed  Google Scholar 

  21. 21

    Just, T., Pau, H. W., Engel, U. & Hummel, T. Cephalic phase insulin release in healthy humans after taste stimulation? Appetite 51, 622–627 (2008).

    Article  CAS  Google Scholar 

  22. 22

    Woods, S. C. et al. Conditioned insulin secretion and meal feeding in rats. J. Comp. Physiol. Psychol. 91, 128–133 (1977).

    Article  CAS  Google Scholar 

  23. 23

    Strubbe, J. H. Parasympathetic involvement in rapid meal-associated conditioned insulin secretion in the rat. Am. J. Physiol. 263, R615–R618 (1992).

    CAS  PubMed  Google Scholar 

  24. 24

    Cohn, C. & Joseph, D. Effects of caloric intake and feeding frequency on carbohydrate metabolism of the rat. J. Nutr. 100, 78–84 (1970).

    Article  CAS  Google Scholar 

  25. 25

    Sugino, T. et al. A transient surge of ghrelin secretion before feeding is modified by different feeding regimens in sheep. Biochem. Biophys. Res. Commun. 298, 785–788 (2002).

    Article  CAS  Google Scholar 

  26. 26

    Drazen, D. L., Vahl, T. P., D'Alessio, D. A., Seeley, R. J. & Woods, S. C. Effects of a fixed meal pattern on ghrelin secretion: evidence for a learned response independent of nutrient status. Endocrinology 147, 23–30 (2006).

    Article  CAS  Google Scholar 

  27. 27

    Shin, Y. K. et al. Ghrelin is produced in taste cells and ghrelin receptor null mice show reduced taste responsivity to salty (NaCl) and sour (citric acid) tastants. PLoS ONE 5, e12729 (2010).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  28. 28

    Tong, J. et al. Ghrelin enhances olfactory sensitivity and exploratory sniffing in rodents and humans. J. Neurosci. 31, 5841–5846 (2011).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  29. 29

    Tschöp, M., Smiley, D. L. & Heiman, M. L. Ghrelin induces adiposity in rodents. Nature 407, 908–913 (2000).

    Article  Google Scholar 

  30. 30

    Vahl, T. P., Drazen, D. L., Seeley, R. J., D'Alessio, D. A. & Woods, S. C. Meal-anticipatory glucagon-like peptide-1 secretion in rats. Endocrinology 151, 569–575 (2010).

    Article  CAS  Google Scholar 

  31. 31

    Martin, B. et al. Modulation of taste sensitivity by GLP-1 signaling in taste buds. Ann. NY Acad. Sci. 1170, 98–101 (2009).

    Article  CAS  Google Scholar 

  32. 32

    Schafmayer, A., Nustede, R., Pompino, A. & Kohler, H. Vagal influence on cholecystokinin and neurotensin release in conscious dogs. Scand. J. Gastroenterol. 23, 315–320 (1988).

    Article  CAS  Google Scholar 

  33. 33

    Secchi, A. et al. Cephalic-phase insulin and glucagon release in normal subjects and in patients receiving pancreas transplantation. Metabolism 44, 1153–1158 (1995).

    Article  CAS  Google Scholar 

  34. 34

    Davidson, A. J. & Stephan, F. K. Plasma glucagon, glucose, insulin, and motilin in rats anticipating daily meals. Physiol. Behav. 1966, 309–315 (1999).

    Article  Google Scholar 

  35. 35

    Taylor, I. L., Feldman, M., Richardson, C. T. & Walsh, J. H. Gastric and cephalic stimulation of human pancreatic polypeptide release. Gastroenterology 75, 432–437 (1978).

    CAS  PubMed  Article  Google Scholar 

  36. 36

    Teff, K. L. Cephalic phase pancreatic polypeptide responses to liquid and solid stimuli in humans. Physiol. Behav. 99, 317–323 (2010).

    Article  CAS  Google Scholar 

  37. 37

    Morricone, L. et al. Food-related sensory stimuli are able to promote pancreatic polypeptide elevation without evident cephalic phase insulin secretion in human obesity. Horm. Metab. Res. 32, 240–245 (2000).

    Article  CAS  Google Scholar 

  38. 38

    Katschinski, M. et al. Cephalic stimulation of gastrointestinal secretory and motor responses in humans. Gastroenterology 103, 383–391 (1992).

    Article  CAS  Google Scholar 

  39. 39

    Liu, M. et al. Diurnal rhythm of apolipoprotein A-IV in rat hypothalamus and its relation to food intake and corticosterone. Endocrinology 145, 3232–3238 (2004).

    Article  CAS  Google Scholar 

  40. 40

    Leahy, J. L. & Fineman, M. S. Impaired phasic insulin and amylin secretion in diabetic rats. Am. J. Physiol. 275, E457–E462 (1998).

    CAS  PubMed  Google Scholar 

  41. 41

    LeBlanc, J. Nutritional implications of cephalic phase thermogenic responses. Appetite 34, 214–216 (2000).

    Article  CAS  Google Scholar 

  42. 42

    de Vries, J., Strubbe, J. H., Wildering, W. C., Gorter, J. A. & Prins, A. J. Patterns of body temperature during feeding in rats under varying ambient temperatures. Physiol. Behav. 53, 229–235 (1993).

    Article  CAS  Google Scholar 

  43. 43

    Katschinski, M. Nutritional implications of cephalic phase gastrointestinal responses. Appetite 34, 189–196 (2000).

    Article  CAS  Google Scholar 

  44. 44

    Konturek, S. J. et al. Brain-gut axis in pancreatic secretion and appetite control. J. Physiol. Pharmacol. 54, 293–317 (2003).

    CAS  PubMed  Google Scholar 

  45. 45

    Weingarten, H. P. & Powley, T. L. Pavlovian conditioning of the cephalic phase of gastric acid secretion in the rat. Physiol. Behav. 27, 217–221 (1981).

    Article  CAS  Google Scholar 

  46. 46

    Feldman, M. & Richardson, C. T. Role of thought, sight, smell, and taste of food in the cephalic phase of gastric acid secretion in humans. Gastroenterology 90, 428–433 (1986).

    Article  CAS  Google Scholar 

  47. 47

    Carneiro, B. T. & Araujo, J. F. Food entrainment: major and recent findings. Front. Behav. Neurosci. 6, 83 (2012).

    Article  PubMed  PubMed Central  Google Scholar 

  48. 48

    Gibbs, J., Young, R. C. & Smith, G. P. Cholecystokinin decreases food intake in rats. J. Comp. Physiol. Psychol. 84, 488–495 (1973).

    Article  CAS  Google Scholar 

  49. 49

    Muurahainenn, N., Kissileff, H. R., Derogatis, A. J. & Pi-Sunyer, F. X. Effects of cholecystokinin-octapeptide (CCK-8) on food intake and gastric emptying in man. Physiol. Behav. 44, 644–649 (1988).

    Article  Google Scholar 

  50. 50

    Lieverse, R. J. et al. Effects of a physiological dose of cholecystokinin on food intake and postprandial satiation in man. Regul. Pept. 43, 83–89 (1993).

    Article  CAS  Google Scholar 

  51. 51

    Beglinger, C., Degen, L., Matzinger, D., D'Amato, M. & Drewe, J. Loxiglumide, a CCK-A receptor antagonist, stimulates calorie intake and hunger feelings in humans. Am. J. Physiol. 280, R1149–R1154 (2001).

    CAS  Google Scholar 

  52. 52

    Moran, T. H., Smith, G. P., Hostetler, A. M. & McHugh, P. R. Transport of cholecystokinin (CCK) binding sites in subdiaphragmatic vagal branches. Brain Res. 415, 149–152 (1987).

    Article  CAS  Google Scholar 

  53. 53

    Abbott, C. R. et al. The inhibitory effects of peripheral administration of peptide YY(3–36) and glucagon-like peptide-1 on food intake are attenuated by ablation of the vagal-brainstem-hypothalamic pathway. Brain Res. 1044, 127–131 (2005).

    Article  CAS  Google Scholar 

  54. 54

    Weatherford, S. C. & Ritter, S. Lesion of vagal afferent terminals impairs glucagon-induced suppression of food intake. Physiol. Behav. 43, 645–650 (1988).

    Article  CAS  Google Scholar 

  55. 55

    Lo, C. C. et al. Apolipoprotein AIV requires cholecystokinin and vagal nerves to suppress food intake. Endocrinology 153, 5857–5865 (2012).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  56. 56

    Koda, S. et al. The role of the vagal nerve in peripheral PYY3-36-induced feeding reduction in rats. Endocrinology 146, 2369–2375 (2005).

    Article  CAS  Google Scholar 

  57. 57

    le Roux, C. W. et al. Ghrelin does not stimulate food intake in patients with surgical procedures involving vagotomy. J. Clin. Endocrinol. Metab. 90, 4521–4524 (2005).

    Article  CAS  Google Scholar 

  58. 58

    Date, Y. et al. The role of the gastric afferent vagal nerve in ghrelin-induced feeding and growth hormone secretion in rats. Gastroenterology 123, 1120–1128 (2002).

    Article  CAS  Google Scholar 

  59. 59

    Lutz, T. A. et al. Lesion of the area postrema/nucleus of the solitary tract (AP/NTS) attenuates the anorectic effects of amylin and calcitonin gene-related peptide (CGRP) in rats. Peptides 19, 309–317 (1998).

    Article  CAS  Google Scholar 

  60. 60

    Hayes, M. R. et al. The common hepatic branch of the vagus is not required to mediate the glycemic and food intake suppressive effects of glucagon-like-peptide-1. Am. J. Physiol. Regul. Integr. Comp. Physiol. 301, R1479–R1485 (2011).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  61. 61

    Kanoski, S. E., Fortin, S. M., Arnold, M., Grill, H. J. & Hayes, M. R. Peripheral and central GLP-1 receptor populations mediate the anorectic effects of peripherally administered GLP-1 receptor agonists, liraglutide and exendin-4. Endocrinology 152, 3103–3112 (2011).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  62. 62

    Arnold, M., Mura, A., Langhans, W. & Geary, N. Gut vagal afferents are not necessary for the eating-stimulatory effect of intraperitoneally injected ghrelin in the rat. J. Neurosci. 26, 11052–11060 (2006).

    Article  CAS  Google Scholar 

  63. 63

    Asakawa, A. et al. Ghrelin is an appetite-stimulatory signal from stomach with structural resemblance to motilin. Gastroenterology 120, 337–345 (2001).

    Article  CAS  Google Scholar 

  64. 64

    Wren, A. M. et al. Ghrelin enhances appetite and increases food intake in humans. J. Clin. Endocrinol. Metab. 86, 5992 (2001).

    Article  CAS  Google Scholar 

  65. 65

    Lo, C. M. et al. Characterization of mice lacking the gene for cholecystokinin. Am. J. Physiol. Regul. Integr. Comp. Physiol. 294, R803–R810 (2008).

    Article  CAS  Google Scholar 

  66. 66

    Scrocchi, L. A., Hill, M. E., Saleh, J., Perkins, B. & Drucker, D. J. Elimination of glucagon-like peptide 1R signaling does not modify weight gain and islet adaptation in mice with combined disruption of leptin and GLP-1 action. Diabetes 49, 1552–1560 (2000).

    Article  CAS  Google Scholar 

  67. 67

    Sun, Y., Ahmed, S. & Smith, R. G. Deletion of ghrelin impairs neither growth nor appetite. Mol. Cell Biol. 23, 7973–7981 (2003).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  68. 68

    Weinstock, P. H. et al. Decreased HDL cholesterol levels but normal lipid absorption, growth, and feeding behavior in apolipoprotein A-IV knockout mice. J. Lipid Res. 38, 1782–1794 (1997).

    CAS  PubMed  Google Scholar 

  69. 69

    Ladenheim, E. E. et al. Disruptions in feeding and body weight control in gastrin-releasing peptide receptor deficient mice. J. Endocrinol. 174, 273–281 (2002).

    Article  CAS  Google Scholar 

  70. 70

    Goodison, T. & Siegel, S. Learning and tolerance to the intake suppressive effect of cholecystokinin in rats. Behav. Neurosci. 109, 62–70 (1995).

    Article  CAS  Google Scholar 

  71. 71

    Duncan, E. A., Davita, G. & Woods, S. C. Changes in the satiating effect of cholecystokinin over repeated trials. Physiol. Behav. 85, 387–393 (2005).

    Article  CAS  Google Scholar 

  72. 72

    Woods, S. C. & Langhans, W. Inconsistencies in the assessment of food intake. Am. J. Physiol. Endocrinol. Metab. 303, E1408–E1418 (2012).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  73. 73

    Sandoval, D. A., Bagnol, D., Woods, S. C., D'Alessio, D. A. & Seeley, R. J. Arcuate GLP-1 receptors regulate glucose homeostasis but not food intake. Diabetes 57, 2046–2054 (2008).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  74. 74

    Williams, D. L., Baskin, D. G. & Schwartz, M. W. Evidence that intestinal glucagon-like peptide-1 plays a physiological role in satiety. Endocrinology 150, 1680–1687 (2009).

    Article  CAS  Google Scholar 

  75. 75

    Flint, A., Raben, A., Astrup, A. & Holst, J. J. Glucagon-like peptide 1 promotes satiety and suppresses energy intake in humans. J. Clin. Invest. 101, 515–520 (1998).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  76. 76

    Morley, J. E. & Levine, A. S. Involvement of dynorphin and the κ opioid receptor in feeding. Peptides 4, 797–800 (1983).

    Article  CAS  Google Scholar 

  77. 77

    Sweet, D. C., Levine, A. S., Billington, C. J. & Kotz, C. M. Feeding response to central orexins. Brain Res. 821, 535–538 (1999).

    Article  CAS  Google Scholar 

  78. 78

    Fujimoto, K., Fukagawa, K., Sakata, T. & Tso, P. Suppression of food intake by apolioprotein A-IV is mediated through the central nervous system in rats. J. Clin. Invest. 91, 1830–1833 (1993).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  79. 79

    Yamada-Goto, N. et al. Intracerebroventricular administration of c-type natriuretic peptide suppresses food intake via activation of the melanocortin system in mice. Diabetes 62, 1500–1504 (2013).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  80. 80

    Hoebel, B. G. Integrative peptides. Brain Res. Bull. 14, 525–528 (1985).

    Article  CAS  Google Scholar 

  81. 81

    Antin, J., Gibbs, J., Holt, J., Young, R. C. & Smith, G. P. Cholecystokinin elicits the complete behavioral sequence of satiety in rats. J. Comp. Physiol. Psychol. 89, 784–790 (1975).

    Article  CAS  Google Scholar 

  82. 82

    West, D. B. et al. Infusion of cholecystokinin between meals into free-feeding rats fails to prolong the intermeal interval. Physiol. Behav. 39, 111–115 (1987).

    Article  CAS  Google Scholar 

  83. 83

    West, D. B., Fey, D. & Woods, S. C. Cholecystokinin persistently suppresses meal size but not food intake in free-feeding rats. Am. J. Physiol. 246, R776–R787 (1984).

    CAS  Google Scholar 

  84. 84

    Bagdade, J. D., Bierman, E. L. & Porte, D. Jr. The significance of basal insulin levels in the evaluation of the insulin response to glucose in diabetic and nondiabetic subjects. J. Clin. Invest. 46, 1549–1557 (1967).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  85. 85

    Lonnqvist, F., Arner, P., Nordfors, L. & Schalling, M. Overexpression of the obest (ob) gene in adipose tissue of human obese subjects. Nat. Med. 1, 950–953 (1995).

    Article  CAS  Google Scholar 

  86. 86

    Baura, G. et al. Saturable transport of insulin from plasma into the central nervous system of dogs in vivo: a mechanism for regulated insulin delivery to the brain. J. Clin. Invest. 92, 1824–1830 (1993).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  87. 87

    Banks, W. A., Kastin, A. J., Huang, W., Jaspan, J. B. & Maness, L. M. Leptin enters the brain by a saturable system independent of insulin. Peptides 17, 305–311 (1996).

    Article  CAS  Google Scholar 

  88. 88

    Maresh, G. A., Maness, L. M., Zadina, J. E. & Kastin, A. J. In vitro demonstration of a saturable transport system for leptin across the blood–brain barrier. Life Sci. 69, 67–73 (2001).

    Article  CAS  Google Scholar 

  89. 89

    Woods, S. C., Lotter, E. C., McKay, L. D. & Porte, D. Jr. Chronic intracerebroventricular infusion of insulin reduces food intake and body weight of baboons. Nature 282, 503–505 (1979).

    Article  CAS  Google Scholar 

  90. 90

    Vogt, M. C. & Bruning, J. C. CNS insulin signaling in the control of energy homeostasis and glucose metabolism—from embryo to old age. Trends Endocrinol. Metab. 24, 76–84 (2013).

    Article  CAS  Google Scholar 

  91. 91

    Campfield, L. A., Smith, F. J., Guisez, Y., Devos, R. & Burn, P. Recombinant mouse OB protein: evidence for a peripheral signal linking adiposity and central neural networks. Science 269, 546–549 (1995).

    Article  CAS  Google Scholar 

  92. 92

    Sindelar, D. K., Mystkowski, P., Marsh, D. J., Palmiter, R. D. & Schwartz, M. W. Attenuation of diabetic hyperphagia in neuropeptide Y-deficient mice. Diabetes 51, 778–783 (2002).

    Article  CAS  Google Scholar 

  93. 93

    Sipols, A. J., Baskin, D. G. & Schwartz, M. W. Effect of intracerebroventricular insulin infusion on diabetic hyperphagia and hypothalamic neuropeptide gene expression. Diabetes 44, 147–151 (1995).

    Article  CAS  Google Scholar 

  94. 94

    Weigle, D. S. et al. Recombinant ob protein reduces feeding and body weight in the ob/ob mouse. J. Clin. Invest. 96, 2065–2070 (1995).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  95. 95

    Benoit, S. C. et al. The catabolic action of insulin in the brain is mediated by melanocortins. J. Neurosci. 22, 9048–9052 (2002).

    Article  CAS  Google Scholar 

  96. 96

    Woods, S. C., Seeley, R. J., Porte, D. Jr & Schwartz, M. W. Signals that regulate food intake and energy homeostasis. Science 280, 1378–1383 (1998).

    Article  CAS  Google Scholar 

  97. 97

    Schwartz, M. W., Woods, S. C., Porte, D. Jr, Seeley, R. J. & Baskin, D. G. Central nervous system control of food intake. Nature 404, 661–671 (2000).

    Article  CAS  Google Scholar 

  98. 98

    Begg, D. P. et al. Reversal of diet-induced obesity increases insulin transport into cerebrospinal fluid and restores sensitivity to the anorexic action of central insulin in male rats. Endocrinology 154, 1047–1054 (2013).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  99. 99

    Zhang, Y. et al. Positional cloning of the mouse obese gene and its human homologue. Nature 372, 425–432 (1994).

    Article  CAS  Google Scholar 

  100. 100

    Bruning, J. C. et al. Role of brain insulin receptor in control of body weight and reproduction. Science 289, 2122–2125 (2000).

    Article  CAS  Google Scholar 

  101. 101

    Morley, J. E. & Flood, J. F. Amylin decreases food intake in mice. Peptides 12, 865–869 (1991).

    Article  CAS  Google Scholar 

  102. 102

    Lutz, T. A. The interaction of amylin with other hormones in the control of eating. Diabetes Obes. Metab. 15, 99–111 (2013).

    Article  CAS  Google Scholar 

  103. 103

    Langhans, W. & Hrupka, B. Interleukins and tumor necrosis factor as inhibitors of food intake. Neuropeptides 33, 415–424 (1999).

    Article  CAS  Google Scholar 

  104. 104

    de Kloet, A. D., Pacheco-Lopez, G., Langhans, W. & Brown, L. M. The effect of TNFα on food intake and central insulin sensitivity in rats. Physiol. Behav. 103, 17–20 (2011).

    Article  CAS  Google Scholar 

  105. 105

    Qi, Y. et al. Adiponectin acts in the brain to decrease body weight. Nat. Med. 10, 524–529 (2004).

    Article  CAS  Google Scholar 

  106. 106

    Hansen, T. K. et al. Weight loss increases circulating levels of ghrelin in human obesity. Clin. Endocrinol. (Oxf.) 56, 203–206 (2002).

    Article  CAS  Google Scholar 

  107. 107

    Dietrich, M. O. & Horvath, T. L. Feeding signals and brain circuitry. Eur. J. Neurosci. 30, 1688–1696 (2009).

    Article  Google Scholar 

  108. 108

    Kirchner, H., Heppner, K. M. & Tschop, M. H. The role of ghrelin in the control of energy balance. Handb. Exp. Pharmacol. 209, 161–184 (2012).

    Article  CAS  Google Scholar 

  109. 109

    Schwartz, G. J., McHugh, P. R. & Moran, T. H. Gastric loads and cholecystokinin synergistically stimulate rat gastric vagal afferents. Am. J. Physiol. 265, R872–R876 (1993).

    CAS  PubMed  Google Scholar 

  110. 110

    Hamilton, R. B. & Norgren, R. Central projections of gustatory nerves in the rat. J. Comp. Neurol. 222, 560–577 (1984).

    Article  CAS  Google Scholar 

  111. 111

    Berthoud, H. R., Carlson, N. R. & Powley, T. L. Topography of efferent vagal innervation of the rat gastrointestinal tract. Am. J. Physiol. 260, R200–R207 (1991).

    CAS  PubMed  Google Scholar 

  112. 112

    Berthoud, H. R., Jedrzejewska, A. & Powley, T. L. Simultaneous labeling of vagal innervation of the gut and afferent projections from the visceral forebrain with dil injected into the dorsal vagal complex in the rat. J. Comp. Neurol. 301, 65–79 (1990).

    Article  CAS  Google Scholar 

  113. 113

    Travagli, R. A., Hermann, G. E., Browning, K. N. & Rogers, R. C. Brainstem circuits regulating gastric function. Annu. Rev. Physiol. 68, 279–305 (2006).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  114. 114

    Grill, H. J. & Hayes, M. R. Hindbrain neurons as an essential hub in the neuroanatomically distributed control of energy balance. Cell. Metab. 16, 296–309 (2012).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  115. 115

    Berthoud, H. R., Sutton, G. M., Townsend, R. L., Patterson, L. M. & Zheng, H. Brainstem mechanisms integrating gut-derived satiety signals and descending forebrain information in the control of meal size. Physiol. Behav. 89, 517–524 (2006).

    Article  CAS  Google Scholar 

  116. 116

    Rinaman, L. Ascending projections from the caudal visceral nucleus of the solitary tract to brain regions involved in food intake and energy expenditure. Brain Res. 1350, 18–34 (2010).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  117. 117

    Schwartz, G. J. Brainstem integrative function in the central nervous system control of food intake. Forum Nutr. 63, 141–151 (2010).

    Article  CAS  Google Scholar 

  118. 118

    Berthoud, H. R., Lenard, N. R. & Shin, A. C. Food reward, hyperphagia, and obesity. Am. J. Physiol. Regul. Integr. Comp. Physiol. 300, R1266–R1277 (2011).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  119. 119

    Kaplan, J. M., Seeley, R. J. & Grill, H. J. Daily caloric intake in intact and chronic decerebrate rats. Behav. Neurosci. 107, 876–881 (1993).

    Article  CAS  Google Scholar 

  120. 120

    Seeley, R. J., Grill, H. J. & Kaplan, J. M. Neurological dissociation of gastrointestinal and metabolic contributions to meal size control. Behav. Neurosci. 108, 347–352 (1994).

    Article  CAS  Google Scholar 

  121. 121

    Grill, H. J. & Smith, G. P. Cholecystokinin decreases sucrose intake in chronic decerebrate rats. Am. J. Physiol. 254, R853–R856 (1988).

    CAS  PubMed  Google Scholar 

  122. 122

    Hayes, M. R., Skibicka, K. P. & Grill, H. J. Caudal brainstem processing is sufficient for behavioral, sympathetic, and parasympathetic responses driven by peripheral and hindbrain glucagon-like-peptide-1 receptor stimulation. Endocrinology 149, 4059–4068 (2008).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  123. 123

    Cota, D. et al. Hypothalamic mTOR signaling regulates food intake. Science 312, 927–930 (2006).

    Article  CAS  Google Scholar 

  124. 124

    Levin, B. E., Magnan, C., Dunn-Meynell, A. & Le Foll, C. Metabolic sensing and the brain: who, what, where, and how? Endocrinology 152, 2552–2557 (2011).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  125. 125

    Guyenet, S. J. & Schwartz, M. W. Clinical review: Regulation of food intake, energy balance, and body fat mass: implications for the pathogenesis and treatment of obesity. J. Clin. Endocrinol. Metab. 97, 745–755 (2012).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  126. 126

    Cone, R. D. et al. The arcuate nucleus as a conduit for diverse signals relevant to energy homeostasis. Int. J. Obes. Relat. Metab. Disord. 25 (Suppl. 5), S63–S67 (2001).

    Article  CAS  Google Scholar 

  127. 127

    Rossi, M. et al. A C-terminal fragment of Agouti-related protein increases feeding and antagonizes the effect of alpha-melanocyte stimulating hormone in vivo. Endocrinology 139, 4428–4431 (1998).

    Article  CAS  Google Scholar 

  128. 128

    Beck, B. Neuropeptide Y in normal eating and in genetic and dietary-induced obesity. Philos. Trans. R. Soc. Lond. B Biol. Sci. 361, 1159–1185 (2006).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  129. 129

    Belgardt, B. F. & Bruning, J. C. CNS leptin and insulin action in the control of energy homeostasis. Ann. NY Acad. Sci. 1212, 97–113 (2010).

    Article  CAS  Google Scholar 

  130. 130

    Williams, K. W. & Elmquist, J. K. From neuroanatomy to behavior: central integration of peripheral signals regulating feeding behavior. Nat. Neurosci. 15, 1350–1355 (2012).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  131. 131

    Mercer, J. G., Moar, K. M. & Hoggard, N. Localization of leptin receptor (Ob-R) messenger ribonucleic acid in the rodent hindbrain. Endocrinology 139, 29–34 (1998).

    Article  CAS  Google Scholar 

  132. 132

    van Houten, M. & Posner, B. I. Specific binding and internalization of blood-borne [125I]-iodoinsulin by neurons of the rat area postrema. Endocrinology 109, 853–859 (1981).

    Article  CAS  Google Scholar 

  133. 133

    Riedy, C. A., Chavez, M., Figlewicz, D. P. & Woods, S. C. Central insulin enhances sensitivity to cholecystokinin. Physiol. Behav. 58, 755–760 (1995).

    Article  CAS  Google Scholar 

  134. 134

    Hallschmid, M., Benedict, C., Born, J., Fehm, H. L. & Kern, W. Manipulating central nervous mechanisms of food intake and body weight regulation by intranasal administration of neuropeptides in man. Physiol. Behav. 83, 55–64 (2004).

    Article  CAS  Google Scholar 

  135. 135

    Sumithran, P. & Proietto, J. The defence of body weight: a physiological basis for weight regain after weight loss. Clin. Sci. (Lond.) 124, 231–241 (2013).

    Article  Google Scholar 

  136. 136

    Edwards, K. L., Stapleton, M., Weis, J. & Irons, B. K. An update in incretin-based therapy: a focus on glucagon-like peptide-1 receptor agonists. Diabetes Technol. Ther. 14, 951–967 (2012).

    Article  CAS  Google Scholar 

  137. 137

    Whitehouse, F. et al. A randomized study and open-label extension evaluating the long-term efficacy of pramlintide as an adjunct to insulin therapy in type 1 diabetes. Diabetes Care 25, 724–730 (2002).

    Article  CAS  Google Scholar 

  138. 138

    Hollander, P. A. et al. Pramlintide as an adjunct to insulin therapy improves long-term glycemic and weight control in patients with type 2 diabetes: a 1-year randomized controlled trial. Diabetes Care 26, 784–790 (2003).

    Article  CAS  Google Scholar 

  139. 139

    Bradley, D. P., Kulstad, R. & Schoeller, D. A. Exenatide and weight loss. Nutrition 26, 243–249 (2010).

    Article  CAS  Google Scholar 

  140. 140

    Younk, L. M., Mikeladze, M. & Davis, S. N. Pramlintide and the treatment of diabetes: a review of the data since its introduction. Expert Opin. Pharmacother. 12, 1439–1451 (2011).

    Article  CAS  PubMed  Google Scholar 

  141. 141

    Pal, R. & Sahu, A. Leptin signaling in the hypothalamus during chronic central leptin infusion. Endocrinology 144, 3789–3798 (2003).

    Article  CAS  Google Scholar 

  142. 142

    Begg, D. P. et al. Reversal of diet-induced obesity increases insulin transport into cerebrospinal fluid and restores sensitivity to the anorexic action of central insulin in male rats. Endocrinology 154, 1047–1054 (2013).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  143. 143

    Clegg, D. J. et al. Consumption of a high-fat diet induces central insulin resistance independent of adiposity. Physiol. Behav. 103, 10–16 (2011).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  144. 144

    El-Haschimi, K., Pierroz, D. D., Hileman, S. M., Bjorbaek, C. & Flier, J. S. Two defects contribute to hypothalamic leptin resistance in mice with diet-induced obesity. J. Clin. Invest. 105, 1827–1832 (2000).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  145. 145

    Born, J. et al. Sniffing neuropeptides: a transnasal approach to the human brain. Nat. Neurosci. 5, 514–516 (2002).

    Article  CAS  Google Scholar 

  146. 146

    Hallschmid, M. et al. Intranasal Insulin reduces body fat in men but not in women. Diabetes 53, 3024–3029 (2004).

    Article  CAS  Google Scholar 

  147. 147

    Proietto, J. & Thorburn, A. W. The therapeutic potential of leptin. Expert Opin. Investig. Drugs 12, 373–378 (2003).

    Article  CAS  Google Scholar 

  148. 148

    Vanderweele, D. A., Haraczkiewicz, E. & Van Itallie, T. B. Elevated insulin and satiety in obese and normal weight rats. Appetite 3, 99–109 (1982).

    Article  CAS  Google Scholar 

  149. 149

    Nicolaidis, S. & Rowland, N. Metering of intravenous versus oral nutrients and regulation of energy balance. Am. J. Physiol. 231, 661–668 (1976).

    Article  CAS  Google Scholar 

  150. 150

    Swinnen, S. G., Simon, A. C., Holleman, F., Hoekstra, J. B. & Devries, J. H. Insulin detemir versus insulin glargine for type 2 diabetes mellitus. Cochrane Database of Systematic Reviews, Issue 1. Art. No.: CD006383. http://dx.doi.org/10.1002/14651858.CD006383.pub2 (2011).

  151. 151

    Zachariah, S. et al. Insulin detemir reduces weight gain as a result of reduced food intake in patients with type 1 diabetes. Diabetes Care 34, 1487–1491 (2011).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  152. 152

    Dornhorst, A. et al. Transferring to insulin detemir from NPH insulin or insulin glargine in type 2 diabetes patients on basal-only therapy with oral antidiabetic drugs improves glycaemic control and reduces weight gain and risk of hypoglycaemia: 14-week follow-up data from PREDICTIVE. Diabetes Obes. Metab. 10, 75–81 (2008).

    CAS  PubMed  Google Scholar 

  153. 153

    Mayer, J. Glucostatic mechanism of regulation of food intake. N. Engl. J. Med. 249, 13–16 (1953).

    Article  CAS  Google Scholar 

  154. 154

    Grossman, S. P. The role of glucose, insulin and glucagon in the regulation of food intake and body weight. Neurosci. Biobehav. Rev. 10, 295–315 (1986).

    Article  CAS  Google Scholar 

  155. 155

    Langhans, W. Metabolic and glucostatic control of feeding. Proc. Nutr. Soc. 55, 497–515 (1996).

    Article  CAS  Google Scholar 

  156. 156

    Faust, I. M. Johnson, P. R. & Hirsch, J. Surgical removal of adipose tissue alters feeding behavior and the development of obesity in rats. Science 197, 393–396 (1977).

    Article  CAS  Google Scholar 

  157. 157

    Shi, H., Strader, A. D., Woods, S. C. & Seeley, R. J. Sexually dimorphic responses to fat loss after caloric restriction or surgical lipectomy. Am. J. Physiol. Endocrinol. Metab. 293, E316–E326 (2007).

    Article  CAS  Google Scholar 

  158. 158

    Benatti, F. et al. Liposuction induces a compensatory increase of visceral fat which is effectively counteracted by physical activity: a randomized trial. J. Clin. Endocrinol. Metab. 97, 2388–2395 (2012).

    Article  CAS  Google Scholar 

  159. 159

    Seeley, R. J., Matson, C. A., Chavez, M., Woods, S. C. & Schwartz, M. W. Behavioral, endocrine and hypothalamic responses to involuntary overfeeding. Am. J. Physiol. 271, R819–R823 (1996).

    Article  CAS  Google Scholar 

  160. 160

    Hagan, M. et al. Role of the CNS melanocortin system in the response to overfeeding. J. Neurosci. 19, 2362–2367 (1999).

    Article  CAS  Google Scholar 

  161. 161

    Sims, E. A. et al. Endocrine and metabolic effects of experimental obesity in man. Recent Prog. Horm. Res. 29, 457–496 (1973).

    CAS  Google Scholar 

  162. 162

    Kennedy, G. C. The hypothalamic control of food intake in rats. Proc. R. Soc. Lond. B Biol. Sci. 137, 535–549 (1950).

    Article  CAS  Google Scholar 

  163. 163

    Sclafani, A., Lucas, F. & Ackroff, K. The importance of taste and palatability in carbohydrate-induced overeating in rats. Am. J. Physiol. 270, R1197–R1202 (1996).

    CAS  PubMed  Google Scholar 

  164. 164

    Ballard, B. D., Gipson, M. T., Guttenberg, W. & Ramsey, K. Palatability of food as a factor influencing obese and normal-weight children's eating habits. Behav. Res. Ther. 18, 598–600 (1980).

    Article  CAS  Google Scholar 

  165. 165

    Tamashiro, K. L. et al. Metabolic and endocrine consequences of social stress in a visible burrow system. Physiol. Behav. 80, 683–693 (2004).

    Article  CAS  Google Scholar 

  166. 166

    de Wit, L. M. et al. Depressive and anxiety disorders and the association with obesity, physical, and social activities. Depress. Anxiety 27, 1057–1065 (2010).

    Article  Google Scholar 

  167. 167

    Goularte, J. F., Ferreira, M. B. & Sanvitto, G. L. Effects of food pattern change and physical exercise on cafeteria diet-induced obesity in female rats. Br. J. Nutr. 108, 1511–1518 (2012).

    Article  CAS  Google Scholar 

  168. 168

    Porikos, K. P. & Pi-Sunyer, F. X. Regulation of food intake in human obesity: studies with caloric dilution and exercise. Clin. Endocrinol. Metab. 13, 547–561 (1984).

    Article  CAS  Google Scholar 

  169. 169

    Peterman, J. N. et al. Relationship between past food deprivation and current dietary practices and weight status among Cambodian refugee women in Lowell, MA. Am. J. Public Health 100, 1930–1937 (2010).

    Article  PubMed  PubMed Central  Google Scholar 

  170. 170

    Swithers, S. E. & Davidson, T. L. Influence of early dietary experience on energy regulation in rats. Physiol. Behav. 86, 669–680 (2005).

    Article  CAS  Google Scholar 

  171. 171

    de Castro, J. M. Prior day's intake has macronutrient-specific delayed negative feedback effects on the spontaneous food intake of free-living humans. J. Nutr. 128, 61–67 (1998).

    Article  CAS  Google Scholar 

  172. 172

    Birch, L. L., Johnson, S. L., Andresen, G., Peters, J. C. & Schulte, M. C. The variability of young children's energy intake. N. Engl. J. Med. 324, 232–235 (1991).

    Article  CAS  Google Scholar 

  173. 173

    Vallerand, A. L., Lupien, J. & Bukowiecki, L. J. Cold exposure reverses the diabetogenic effects of high-fat feeding. Diabetes 35, 329–334 (1986).

    Article  CAS  Google Scholar 

  174. 174

    Dunlap, S. & Heinrichs, S. C. Neuronal depletion of omega-3 fatty acids induces flax seed dietary self-selection in the rat. Brain Res. 1250, 113–119 (2009).

    Article  CAS  Google Scholar 

  175. 175

    Rozin, P. Are carbohydrate and protein intakes separately regulated. J. Comp. Physiol. Psychol. 65, 23–29 (1968).

    Article  CAS  Google Scholar 

  176. 176

    Berthoud, H. R. The neurobiology of food intake in an obesogenic environment. Proc. Nutr. Soc. 71, 478–487 (2012).

    Article  PubMed  PubMed Central  Google Scholar 

  177. 177

    Berthoud, H. R. Metabolic and hedonic drives in the neural control of appetite: who is the boss? Curr. Opin. Neurobiol. 21, 888–896 (2011).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  178. 178

    Chrousos, G. P. Stress and disorders of the stress system. Nat. Rev. Endocrinol. 5, 374–381 (2009).

    Article  CAS  Google Scholar 

  179. 179

    Ulrich-Lai, Y. M. & Herman, J. P. Neural regulation of endocrine and autonomic stress responses. Nat. Rev. Neurosci. 10, 397–409 (2009).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  180. 180

    Maniam, J. & Morris, M. J. The link between stress and feeding behaviour. Neuropharmacology 63, 97–110 (2012).

    Article  CAS  Google Scholar 

  181. 181

    Dallman, M. F. Stress-induced obesity and the emotional nervous system. Trends Endocrinol. Metab. 21, 159–165 (2010).

    Article  CAS  Google Scholar 

  182. 182

    Adam, T. C. & Epel, E. S. Stress, eating and the reward system. Physiol. Behav. 91, 449–458 (2007).

    Article  CAS  Google Scholar 

  183. 183

    Schwartz, M. W., Dallman, M. F. & Woods, S. C. The hypothalamic response to starvation: implications for the study of wasting disorders. Am. J. Physiol. 269, R949–R957 (1995).

    CAS  PubMed  Google Scholar 

  184. 184

    Seeley, R. J. et al. Behavioral, endocrine, and hypothalamic responses to involuntary overfeeding. Am. J. Physiol. 271, R819–R823 (1996).

    Article  CAS  Google Scholar 

  185. 185

    Hanson, E. S. & Dallman, M. F. Neuropeptide Y (NPY) may integrate responses of hypothalamic feeding systems and the hypothalamo-pituitary-adrenal axis. J. Neuroendocrinol. 7, 273–279 (1995).

    Article  CAS  Google Scholar 

  186. 186

    Strack, A. M., Sebastian, R. J., Schwartz, M. W. & Dallman, M. F. Glucocorticoids and insulin: reciprocal signals for energy balance. Am. J. Physiol. 268, 142–149 (1995).

    Google Scholar 

  187. 187

    Glowa, J. & Gold, P. Corticotropin releasing hormone produces profound anorexigenic effects in the rhesus monkey. Neuropeptides 18, 55–61 (1991).

    Article  CAS  Google Scholar 

  188. 188

    Richard, D., Huang, Q. & Timofeeva, E. The corticotropin-releasing hormone system in the regulation of energy balance in obesity. Int. J. Obes. Relat. Metab. Disord. 24, S36–S39 (2000).

    Article  CAS  Google Scholar 

  189. 189

    Green, P. K., Wilkinson, C. W. & Woods, S. C. Intraventricular corticosterone increases the rate of body weight gain in underweight adrenalectomized rats. Endocrinology 130, 269–275 (1992).

    Article  CAS  Google Scholar 

  190. 190

    Zakrzewska, K. E. et al. Induction of obesity and hyperleptinemia by central glucocorticoid infusion in the rat. Diabetes 48, 365–370 (1999).

    Article  CAS  Google Scholar 

  191. 191

    White, B. D., Dean, R. G. & Martin, R. J. Adrenalectomy decreases neuropeptide Y mRNA levels in the arcuate nucleus. Brain Res. Bull. 25, 711–715 (1990).

    Article  CAS  Google Scholar 

  192. 192

    Dallman, M. F., Akana, S. F., Strack, A. M., Hanson, E. S. & Sebastian, R. J. The neural network that regulates energy balance is responsive to glucocorticoids and insulin and also regulates HPA axis responsivity at a site proximal to CRF neurons. Ann. NY Acad. Sci. 771, 730–742 (1995).

    Article  CAS  Google Scholar 

  193. 193

    Zakrzewska, K. E. et al. Selective dependence of intracerebroventricular neuropeptide Y-elicited effects on central glucocorticoids. Endocrinology 140, 3183–3187 (1999).

    Article  CAS  Google Scholar 

  194. 194

    Jahng, J. W. et al. Dexamethasone reduces food intake, weight gain and the hypothalamic 5-HT concentration and increases plasma leptin in rats. Eur. J. Pharmacol. 581, 64–70 (2008).

    Article  CAS  Google Scholar 

  195. 195

    Miell, J. P., Englaro, P. & Blum, W. F. Dexamethasone induces an acute and sustained rise in circulating leptin levels in normal human subjects. Horm. Metab. Res. 28, 704–707 (1996).

    Article  CAS  Google Scholar 

  196. 196

    Mostyn, A., Keisler, D. H., Webb, R., Stephenson, T. & Symonds, M. E. The role of leptin in the transition from fetus to neonate. Proc. Nutr. Soc. 60, 187–194 (2001).

    Article  CAS  Google Scholar 

  197. 197

    Fried, S. K., Russell, C. D., Grauso, N. L. & Brolin, R. E. Lipoprotein lipase regulation by insulin and glucocorticoid in subcutaneous and omental adipose tissues of obese women and men. J. Clin. Invest. 92, 2191–2198 (1993).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  198. 198

    Nieuwenhuizen, A. G. & Rutters, F. The hypothalamic–pituitary–adrenal–axis in the regulation of energy balance. Physiol. Behav. 94, 169–177 (2008).

    Article  CAS  Google Scholar 

  199. 199

    Chuang, J. C. et al. Ghrelin mediates stress-induced food-reward behavior in mice. J. Clin. Invest. 121, 2684–2692 (2011).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  200. 200

    Disse, E. et al. Peripheral ghrelin enhances sweet taste food consumption and preference, regardless of its caloric content. Physiol. Behav. 101, 277–281 (2010).

    Article  CAS  Google Scholar 

  201. 201

    Richardson, R. D., Omachi, K., Kermani, R. & Woods, S. C. Intraventricular insulin potentiates the anorexic effect of corticotropin releasing hormone in rats. Am. J. Physiol. Regul. Integr. Comp. Physiol. 283, R1321–R1326 (2002).

    Article  CAS  Google Scholar 

  202. 202

    Bello, N. T. & Hajnal, A. Dopamine and binge eating behaviors. Pharmacol. Biochem. Behav. 97, 25–33 (2010).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  203. 203

    Foster, M. T. et al. Palatable foods, stress, and energy stores sculpt corticotropin-releasing factor, adrenocorticotropin, and corticosterone concentrations after restraint. Endocrinology 150, 2325–2333 (2009).

    Article  CAS  Google Scholar 

  204. 204

    Dallman, M. F. et al. Chronic stress and obesity: a new view of “comfort food”. Proc. Natl Acad. Sci. USA 100, 11696–11701 (2003).

    Article  CAS  Google Scholar 

  205. 205

    Ulrich-Lai, Y. M. et al. Pleasurable behaviors reduce stress via brain reward pathways. Proc. Natl Acad. Sci. USA 107, 20529–20534 (2010).

    Article  Google Scholar 

  206. 206

    Bhatnagar, S. et al. Corticosterone facilitates saccharin intake in adrenalectomized rats: does corticosterone increase stimulus salience? J. Neuroendocrinol. 12, 453–460 (2000).

    Article  CAS  Google Scholar 

  207. 207

    Clegg, D. J. Minireview: the year in review of estrogen regulation of metabolism. Mol. Endocrinol. 26, 1957–1960 (2012).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  208. 208

    Brown, L. M., Gent, L., Davis, K. & Clegg, D. J. Metabolic impact of sex hormones on obesity. Brain Res. 1350, 77–85 (2010).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  209. 209

    Asarian, L. & Geary, N. Estradiol enhances cholecystokinin-dependent lipid-induced satiation and activates estrogen receptor-alpha-expressing cells in the nucleus tractus solitarius of ovariectomized rats. Endocrinology 148, 5656–5666 (2007).

    Article  CAS  Google Scholar 

  210. 210

    Thammacharoen, S., Lutz, T. A., Geary, N. & Asarian, L. Hindbrain administration of estradiol inhibits feeding and activates estrogen receptor-alpha-expressing cells in the nucleus tractus solitarius of ovariectomized rats. Endocrinology 149, 1609–1617 (2008).

    Article  CAS  Google Scholar 

  211. 211

    Buffenstein, R., Poppitt, S. D., McDevitt, R. M. & Prentice, A. M. Food intake and the menstrual cycle: a retrospective analysis, with implications for appetite research. Physiol. Behav. 58, 1067–1077 (1995).

    Article  CAS  Google Scholar 

  212. 212

    Asarian, L. & Geary, N. Modulation of appetite by gonadal steroid hormones. Philos. Trans. R. Soc. Lond. B Biol. Sci. 361, 1251–1263 (2006).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  213. 213

    Xu, Y. et al. Distinct hypothalamic neurons mediate estrogenic effects on energy homeostasis and reproduction. Cell. Metab. 14, 453–465 (2011).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  214. 214

    Chai, J. K. et al. Use of orchiectomy and testosterone replacement to explore meal number-to-meal size relationship in male rats. Am. J. Physiol. 276, R1366–R1373 (1999).

    CAS  PubMed  Google Scholar 

  215. 215

    Putnam, K., Shoemaker, R., Yiannikouris, F. & Cassis, L. A. The renin-angiotensin system: a target of and contributor to dyslipidemias, altered glucose homeostasis, and hypertension of the metabolic syndrome. Am. J. Physiol. Heart Circ. Physiol. 302, H1219–H1230 (2012).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  216. 216

    Epstein, A. N., Fitzsimons, J. T. & Simons, B. J. Drinking caused by the intracranial injection of angiotensin into the rat. J. Physiol. 200, 98P–100P (1969).

    CAS  PubMed  Google Scholar 

  217. 217

    Abraham, S. F., Denton, D. A. & Weisinger, R. S. The specificity of the dipsogenic effect of angiotensin II. Pharmacol. Biochem. Behav. 4, 363–368 (1976).

    Article  CAS  Google Scholar 

  218. 218

    Giacchetti, G. et al. Overexpression of the renin-angiotensin system in human visceral adipose tissue in normal and overweight subjects. Am. J. Hypertens. 15, 381–388 (2002).

    Article  CAS  Google Scholar 

  219. 219

    Harte, A. L. et al. Insulin increases angiotensinogen expression in human abdominal subcutaneous adipocytes. Diabetes Obes. Metab. 5, 462–467 (2003).

    Article  CAS  Google Scholar 

  220. 220

    Iwashita, M. et al. Valsartan, independently of AT1 receptor or PPARγ, suppresses LPS-induced macrophage activation and improves insulin resistance in cocultured adipocytes. Am. J. Physiol. Endocrinol. Metab. 302, E286–E296 (2012).

    Article  CAS  Google Scholar 

  221. 221

    Massiera, F. et al. Adipose angiotensinogen is involved in adipose tissue growth and blood pressure regulation. FASEB J. 15, 2727–2729 (2001).

    Article  CAS  Google Scholar 

  222. 222

    Weisinger, R. S., Begg, D. P. & Jois, M. Antagonists of the renin-angiotensin system and the prevention of obesity. Curr. Opin. Investig. Drugs 10, 1069–1077 (2009).

    CAS  PubMed  Google Scholar 

  223. 223

    Jayasooriya, A. P. et al. Mice lacking angiotensin-converting enzyme have increased energy expenditure, with reduced fat mass and improved glucose clearance. Proc. Natl Acad. Sci. USA 105, 6531–6536 (2008).

    Article  CAS  Google Scholar 

  224. 224

    Massiera, F. et al. Angiotensinogen-deficient mice exhibit impairment of diet-induced weight gain with alteration in adipose tissue development and increased locomotor activity. Endocrinology 142, 5220–5225 (2001).

    Article  CAS  Google Scholar 

  225. 225

    Fitzsimons, J. T. Angiotensin, thirst, and sodium appetite. Physiol. Rev. 78, 583–686 (1998).

    Article  CAS  Google Scholar 

  226. 226

    Miselis, R. R. The efferent projections of the subfornical organ of the rat: a circumventricular organ within a neural network subserving water balance. Brain Res. 230, 1–23 (1981).

    Article  CAS  Google Scholar 

  227. 227

    de Kloet, A. D. et al. Angiotensin type 1a receptors in the paraventricular nucleus of the hypothalamus protect against diet-induced obesity. J. Neurosci. 33, 4825–4833 (2013).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  228. 228

    Yamamoto, R. et al. Angiotensin II type 1 receptor signaling regulates feeding behavior through anorexigenic corticotropin-releasing hormone in hypothalamus. J. Biol. Chem. 286, 21458–21465 (2011).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  229. 229

    Enalapril in essential hypertension: a comparative study with propranolol. Enalapril in Hypertension Study Group (UK). Br. J. Clin. Pharmacol. 18, 51–56 (1984).

  230. 230

    de Kloet, A. D., Krause, E. G. & Woods, S. C. The renin angiotensin system and the metabolic syndrome. Physiol. Behav. 100, 525–534 (2010).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  231. 231

    Minamino, N., Makino, Y., Tateyama, H., Kangawa, K. & Matsuo, H. Characterization of immunoreactive human C-type natriuretic peptide in brain and heart. Biochem. Biophys. Res. Commun. 179, 535–542 (1991).

    Article  CAS  Google Scholar 

  232. 232

    Bartels, E. D., Nielsen, J. M., Bisgaard, L. S., Goetze, J. P. & Nielsen, L. B. Decreased expression of natriuretic peptides associated with lipid accumulation in cardiac ventricle of obese mice. Endocrinology 151, 5218–5225 (2010).

    Article  CAS  Google Scholar 

  233. 233

    Inuzuka, M. et al. C-type natriuretic peptide as a new regulator of food intake and energy expenditure. Endocrinology 151, 3633–3642 (2010).

    Article  CAS  Google Scholar 

  234. 234

    Gray, J. M. et al. Oxygen sensation and social feeding mediated by a C. elegans guanylate cyclase homologue. Nature 430, 317–322 (2004).

    Article  CAS  PubMed  Google Scholar 

  235. 235

    Valentino, M. A. et al. A uroguanylin-GUCY2C endocrine axis regulates feeding in mice. J. Clin. Invest. 121, 3578–3588 (2011).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  236. 236

    Berkseth, K. E., Schur, E. & Schwartz, M. W. A role for natriuretic peptides in the central control of energy balance? Diabetes 62, 1379–1381 (2013).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  237. 237

    Ehrlich, K. J. & Fitts, D. A. Atrial natriuretic peptide in the subfornical organ reduces drinking induced by angiotensin or in response to water deprivation. Behav. Neurosci. 104, 365–372 (1990).

    Article  CAS  Google Scholar 

  238. 238

    Villarreal, D., Freeman, R. H., Davis, J. O., Verburg, K. M. & Vari, R. C. Renal mechanisms for suppression of renin secretion by atrial natriuretic factor. Hypertension 8, II28–II35 (1986).

    Article  CAS  Google Scholar 

  239. 239

    Brolin, R. E., Robertson, L. B., Kenler, H. A. & Cody, R. P. Weight loss and dietary intake after vertical banded gastroplasty and Roux-en-Y gastric bypass. Ann. Surg. 220, 782–790 (1994).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  240. 240

    Kenler, H. A., Brolin, R. E. & Cody, R. P. Changes in eating behavior after horizontal gastroplasty and Roux-en-Y gastric bypass. Am. J. Clin. Nutr. 52, 87–92 (1990).

    Article  CAS  Google Scholar 

  241. 241

    Ullrich, J., Ernst, B., Wilms, B., Thurnheer, M. & Schultes, B. Roux-en-Y gastric bypass surgery reduces hedonic hunger and improves dietary habits in severely obese subjects. Obes. Surg. 23, 50–55 (2013).

    Article  Google Scholar 

  242. 242

    Chambers, A. P. et al. Weight-independent changes in blood glucose homeostasis after gastric bypass or vertical sleeve gastrectomy in rats. Gastroenterology 141, 950–958 (2011).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  243. 243

    Liou, A. P. et al. Conserved shifts in the gut microbiota due to gastric bypass reduce host weight and adiposity. Sci. Transl Med. 5, 178ra141 (2013).

    Article  CAS  Google Scholar 

  244. 244

    Shin, A. C., Zheng, H., Townsend, R. L., Sigalet, D. L. & Berthoud, H. R. Meal-induced hormone responses in a rat model of Roux-en-Y gastric bypass surgery. Endocrinology 151, 1588–1597 (2010).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  245. 245

    Stefater, M. A. et al. Sleeve gastrectomy induces loss of weight and fat mass in obese rats, but does not affect leptin sensitivity. Gastroenterology 138, 2426–2436 (2010).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  246. 246

    Wilson-Perez, H. E. et al. The effect of vertical sleeve gastrectomy on food choice in rats. Int. J. Obes. (Lond.) 37, 288–295 (2013).

    Article  CAS  Google Scholar 

  247. 247

    Lingvay, I., Guth, E., Islam, A. & Livingston, E. Rapid improvement of diabetes after gastric bypass surgery: is it the diet or surgery? Diabetes Care http://dx.doi.org/10.2337/dc12-2316.

  248. 248

    Stefater, M. A., Wilson-Perez, H. E., Chambers, A. P., Sandoval, D. A. & Seeley, R. J. All bariatric surgeries are not created equal: insights from mechanistic comparisons. Endocr. Rev. 33, 595–622 (2012).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  249. 249

    Korner, J. et al. Effects of Roux-en-Y gastric bypass surgery on fasting and postprandial concentrations of plasma ghrelin, peptide YY, and insulin. J. Clin. Endocrinol. Metab. 90, 359–365 (2005).

    Article  CAS  Google Scholar 

  250. 250

    le Roux, C. W. et al. Gut hormone profiles following bariatric surgery favor an anorectic state, facilitate weight loss, and improve metabolic parameters. Ann. Surg. 243, 108–114 (2006).

    Article  Google Scholar 

  251. 251

    Ramon, J. M. et al. Effect of Roux-en-Y gastric bypass vs sleeve gastrectomy on glucose and gut hormones: a prospective randomised trial. J. Gastrointest. Surg. 16, 1116–1122 (2012).

    Article  Google Scholar 

  252. 252

    Warde-Kamar, J., Rogers, M., Flancbaum, L. & Laferrere, B. Calorie intake and meal patterns up to 4 years after Roux-en-Y gastric bypass surgery. Obes. Surg. 14, 1070–1079 (2004).

    Article  Google Scholar 

  253. 253

    Stemmer, K. et al. Roux-en-Y gastric bypass surgery but not vertical sleeve gastrectomy decreases bone mass in male rats. Endocrinology 154, 2015–2024 (2013).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  254. 254

    Pournaras, D. J. & le Roux, C. W. The effect of bariatric surgery on gut hormones that alter appetite. Diabetes Metab. 35, 508–512 (2009).

    Article  CAS  Google Scholar 

  255. 255

    Chambers, A. P. et al. The effects of vertical sleeve gastrectomy in rodents are ghrelin independent. Gastroenterology 144, 50–52 e55 (2013).

    Article  CAS  Google Scholar 

  256. 256

    Wilson-Perez, H. E. et al. Vertical sleeve gastrectomy is effective in two genetic mouse models of glucagon-like peptide-1 receptor deficiency. Diabetes 62, 2380–2385 (2013).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  257. 257

    Cano, V., Merino, B., Ezquerra, L., Somoza, B. & Ruiz-Gayo, M. A cholecystokinin-1 receptor agonist (CCK-8) mediates increased permeability of brain barriers to leptin. Br. J. Pharmacol. 154, 1009–1015 (2008).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  258. 258

    Kohli, R. et al. Intestinal adaptation after ileal interposition surgery increases bile acid recycling and protects against obesity-related comorbidities. Am. J. Physiol. Gastrointest. Liver Physiol. 299, G652–G660 (2010).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  259. 259

    Haluzikova, D. et al. Laparoscopic sleeve gastrectomy differentially affects serum concentrations of FGF-19 and FGF-21 in morbidly obese subjects. Obesity (Silver Spring) http://dx.doi.org/10.1002/oby.20208.

  260. 260

    Ryan, K. K. et al. Fibroblast growth factor-19 action in the brain reduces food intake and body weight and improves glucose tolerance in male rats. Endocrinology 154, 9–15 (2013).

    Article  CAS  Google Scholar 

  261. 261

    Xu, H. et al. Chronic inflammation in fat plays a crucial role in the development of obesity-related insulin resistance. J. Clin. Invest. 112, 1821–1830 (2003).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  262. 262

    Shoelson, S. E., Lee, J. & Goldfine, A. B. Inflammation and insulin resistance. J. Clin. Invest. 116, 1793–1801 (2006).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  263. 263

    Lumeng, C. N., Bodzin, J. L. & Saltiel, A. R. Obesity induces a phenotypic switch in adipose tissue macrophage polarization. J. Clin. Invest. 117, 175–184 (2007).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  264. 264

    Premaratna, S. D. et al. Angiotensin-converting enzyme inhibition reverses diet-induced obesity, insulin resistance and inflammation in C57BL/6J mice. Int. J. Obes (Lond.) 36, 233–243 (2012).

    Article  CAS  Google Scholar 

  265. 265

    Hotamisligil, G. S. Inflammatory pathways and insulin action. Int. J. Obes. Relat. Metab. Disord. 27 (Suppl. 3), S53–S55 (2003).

    Article  CAS  Google Scholar 

  266. 266

    Fantino, M. & Wieteska, L. Evidence for a direct central anorectic effect of tumor-necrosis-factor-α in the rat. Physiol. Behav. 53, 477–483 (1993).

    Article  CAS  Google Scholar 

  267. 267

    Bernstein, I. L., Taylor, E. M. & Bentson, K. L. TNF-induced anorexia and learned food aversions are attenuated by area postrema lesions. Am. J. Physiol. 260, R906–R910 (1991).

    CAS  PubMed  Google Scholar 

  268. 268

    Plata-Salaman, C. R., Oomura, Y. & Kai, Y. Tumor necrosis factor and interleukin-1B: suppression of food intake by direct action in the central nervous system. Brain Res. 448, 106–114 (1988).

    Article  CAS  Google Scholar 

  269. 269

    Smith, B. K. & Kluger, M. J. Anti-TNF-α antibodies normalized body temperature and enhanced food intake in tumor-bearing rats. Am. J. Physiol. 265, R615–R619 (1993).

    CAS  PubMed  Google Scholar 

  270. 270

    Bluthe, R. M. et al. Synergy between tumor necrosis factor alpha and interleukin-1 in the induction of sickness behavior in mice. Psychoneuroendocrinology 19, 197–207 (1994).

    Article  CAS  Google Scholar 

  271. 271

    De Souza, C. T. et al. Consumption of a fat-rich diet activates a proinflammatory response and induces insulin resistance in the hypothalamus. Endocrinology 146, 4192–4199 (2005).

    Article  CAS  Google Scholar 

  272. 272

    Thaler, J. P. et al. Obesity is associated with hypothalamic injury in rodents and humans. J. Clin. Invest. 122, 153–162 (2012).

    Article  Google Scholar 

Download references

Author information

Affiliations

Authors

Contributions

Both authors contributed equally to all aspects of this manuscript.

Corresponding author

Correspondence to Stephen C. Woods.

Ethics declarations

Competing interests

The authors declare no competing financial interests.

Rights and permissions

Reprints and Permissions

About this article

Cite this article

Begg, D., Woods, S. The endocrinology of food intake. Nat Rev Endocrinol 9, 584–597 (2013). https://doi.org/10.1038/nrendo.2013.136

Download citation

Further reading

Search

Nature Briefing

Sign up for the Nature Briefing newsletter — what matters in science, free to your inbox daily.

Get the most important science stories of the day, free in your inbox. Sign up for Nature Briefing