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Different forms of obesity as a function of diet composition

Abstract

OBJECTIVE:

To characterize the phenotype of obesity on a high-carbohydrate diet (HCD) as compared to a high-fat diet (HFD) or moderate-fat diet (MFD).

METHODS AND PROCEDURES:

In four experiments, adult Sprague–Dawley rats (275–300 g) were maintained for several weeks on a: (1) HFD with 50% fat; (2) balanced MFD with 25% fat; or (3) HCD with 10% fat/65% carbohydrate. Then, based on the amount of body fat accumulated in four dissected fat pads, the animals were subgrouped as lean (lowest tertile) or obese (highest tertile) and characterized with multiple measures.

RESULTS:

The obese rats of these diet groups, with 70–80% greater body fat than the lean animals, exhibited elevated levels of leptin and insulin and increased activity of lipoprotein lipase in adipose tissue (aLPL), with no change in muscle LPL. Characteristics common to the obese rats on the HFD or MFD, but not seen on the HCD, were hyperphagia, elevated circulating levels of triglycerides (TG), nonesterified fatty acids (NEFA) and glucose, and a significant increase in β-hydroxyacyl-CoA dehydrogenase (HADH) activity in muscle, reflecting its greater capacity to metabolize fat. This was accompanied by a significant increase in expression of the peptide, galanin (GAL), in the paraventricular nucleus (PVN), as measured by in situ hybridization and real-time quantitative PCR, and also in GAL peptide immunoreactivity. These measures of GAL were consistently, positively correlated with circulating TG levels and also with HADH activity in muscle. In contrast to these fat-associated changes, rats that became obese on an HCD maintained normal caloric intake and levels of TG, NEFA, and glucose. They also showed no change in PVN GAL mRNA or peptide. Instead, they exhibited a significant reduction in HADH activity compared to the lean animals, along with increased activity of phosphofructokinase in muscle, a key enzyme in glycolysis.

CONCLUSION:

Specific characteristics of obesity, including expression of hypothalamic peptides, are dependent upon diet composition. Whereas obesity on an HFD is associated with hyperphagia and elevated lipids, fat metabolism in muscle, and fat-stimulated peptides such as GAL, obesity on an HCD with a similar increase in body fat shows none of these characteristics and instead exhibits a metabolic pattern in muscle that favors carbohydrate over fat oxidation. These results suggest the existence of multiple forms of obesity with different underlying mechanisms that are diet dependent.

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References

  1. Hill JO, Melanson EL, Wyatt HT . Dietary fat intake and regulation of energy balance: implications for obesity. J Nutr 2000; 130: 284S–288S.

    Article  CAS  Google Scholar 

  2. West DB, York B . Dietary fat, genetic predisposition, and obesity: lessons from animal models. Am J Clin Nutr 1998; 67: 505S–512S.

    Article  CAS  Google Scholar 

  3. Golay A, Bobbioni E . The role of dietary fat in obesity. Int J Obes Relat Metab Disord 1997; 21: S2–S11.

    Google Scholar 

  4. Wang J, Alexander JT, Zheng P, Yu HJ, Dourmashkin J, Leibowitz SF . Behavioral and endocrine traits of obesity-prone and obesity-resistant rats on macronutrient diets. Am J Physiol 1998; 274: E1057–E1066.

    Article  CAS  Google Scholar 

  5. Buettner R, Newgard CB, Rhodes CJ, O'Doherty RM . Correction of diet-induced hyperglycemia, hyperinsulinemia, and skeletal muscle insulin resistance by moderate hyperleptinemia. Am J Physiol Endocrinol Metab 2000; 278: E563–E569.

    Article  CAS  Google Scholar 

  6. Leibowitz SF, Dourmashkin JT, Chang GQ, Hill JO, Gayles EC, Fried SK, Wang J . Acute high-fat diet paradigms link galanin to triglycerides and their transport and metabolism in muscle. Brain Res 2004; 1008: 168–178.

    Article  CAS  Google Scholar 

  7. Nagase H, Bray GA, York DA . Effect of galanin and enterostatin on sympathetic nerve activity to interscapular brown adipose tissue. Brain Res 1996; 709: 44–50.

    Article  CAS  Google Scholar 

  8. Nemeth PM, Rosser BW, Choksi RM, Norris BJ, Baker KM . Metabolic response to a high-fat diet in neonatal and adult rat muscle. Am J Physiol 1992; 262: C282–C286.

    Article  CAS  Google Scholar 

  9. Ludwig DS . Dietary glycemic index and obesity. J Nutr 2000; 130: 280S–283S.

    Article  CAS  Google Scholar 

  10. Brand-Miller JC, Holt SH, Pawlak DB, McMillan J . Glycemic index and obesity. Am J Clin Nutr 2002; 76: 281S–285S.

    Article  CAS  Google Scholar 

  11. Leibowitz SF, Akabayashi A, Wang J . Obesity on a high-fat diet: role of hypothalamic galanin in neurons of the anterior paraventricular nucleus projecting to the median eminence. J Neurosci 1998; 18: 2709–2719.

    Article  CAS  Google Scholar 

  12. Ramirez R, Lopez JM, Bedoya FJ, Goberna R . Effects of high-carbohydrate or high-fat diet on carbohydrate metabolism and insulin secretion in the normal rat. Diabet Res 1990; 15: 179–183.

    CAS  Google Scholar 

  13. Sclafani A . Carbohydrate taste, appetite, and obesity: an overview. Neurosci Biobehav Rev 1987; 11: 131–153.

    Article  CAS  Google Scholar 

  14. Oscai LB, Miller WC, Arnall DA . Effects of dietary sugar and of dietary fat on food intake and body fat content in rats. Growth 1987; 51: 64–73.

    CAS  PubMed  Google Scholar 

  15. Kanarek RB, Marks-Kaufman R . Developmental aspects of sucrose-induced obesity in rats. Physiol Behav 1979; 23: 881–885.

    Article  CAS  Google Scholar 

  16. Kersten S . Mechanisms of nutritional and hormonal regulation of lipogenesis. EMBO Rep 2001; 2: 282–286.

    Article  CAS  Google Scholar 

  17. Hirschberg AL . Hormonal regulation of appetite and food intake. Ann Med 1998; 30: 7–20.

    Article  CAS  Google Scholar 

  18. Minshull M, Strong CR . The stimulation of lipogenesis in white adipose tissue from fed rats by corticosterone. Int J Biochem 1985; 17: 529–532.

    Article  CAS  Google Scholar 

  19. Wang J, Dourmashkin JT, Yun R, Leibowitz SF . Rapid changes in hypothalamic neuropeptide Y produced by carbohydrate-rich meals that enhance corticosterone and glucose levels. Brain Res 1999; 848: 124–136.

    Article  CAS  Google Scholar 

  20. Wang J, Akabayashi A, Dourmashkin J, Yu HJ, Alexander JT, Chae HJ, Leibowitz SF . Neuropeptide Y in relation to carbohydrate intake, corticosterone, and dietary obesity. Brain Res 1998; 802: 75–88.

    Article  CAS  Google Scholar 

  21. Giraudo SQ, Kotz CM, Grace MK, Levine AS, Billington CJ . Rat hypothalamic NPY mRNA and brown fat uncoupling protein mRNA after high-carbohydrate or high-fat diets. Am J Physiol 1994; 266: R1578–R1583.

    CAS  PubMed  Google Scholar 

  22. Wang H, Storlien LH, Huang XF . Effects of dietary fat types on body fatness, leptin, and ARC leptin receptor, NPY, and AgRP mRNA expression. Am J Physiol Endocrinol Metab 2002; 282: E1352–E1359.

    Article  CAS  Google Scholar 

  23. Xue CY, Kageyama H, Kashiba M, Kobayashi A, Osaka T, Namba Y, Kimura S, Inoue S . Different origin of hypertriglyceridemia induced by a high-fat and a high-sucrose diet in ventromedial hypothalamic-lesioned obese and normal rats. Int J Obes Relat Metab Disord 2001; 25: 434–438.

    Article  CAS  Google Scholar 

  24. Stern JS, Johnson PR, Batchelor BR, Zucker LM, Hirsch J . Pancreatic insulin release and peripheral tissue resistance in Zucker obese rats fed high- and low-carbohydrate diets. Am J Physiol 1975; 228: 543–548.

    Article  CAS  Google Scholar 

  25. Schemmel RA, Teague RJ, Bray GA . Obesity in Osborne-Mendel and S 5B/Pl rats: effects of sucrose solutions, castration, and treatment with estradiol or insulin. Am J Physiol 1982; 243: R347–R353.

    CAS  PubMed  Google Scholar 

  26. Surwit RS, Feinglos MN, Rodin J, Sutherland A, Petro AE, Opara EC, Kuhn CM, Rebuffe-Scrive M . Differential effects of fat and sucrose on the development of obesity and diabetes in C57BL/6J and A/J mice. Metabolism 1995; 44: 645–651.

    Article  CAS  Google Scholar 

  27. Yamini S, Staples RC, Hansen CT, Szepesi B . Effect of dietary carbohydrate on liver and kidney enzyme activities and plasma amino acids in the LA/N-cp rat. Int J Obes 1991; 15: 189–203.

    CAS  PubMed  Google Scholar 

  28. Le Stunff C, Bougneres PF . Time course of increased lipid and decreased glucose oxidation during early phase of childhood obesity. Diabetes 1993; 42: 1010–1016.

    Article  CAS  Google Scholar 

  29. Leibowitz SF, Wortley KE . Hypothalamic control of energy balance: different peptides, different functions. Peptides 2004; 25: 473–504.

    Article  CAS  Google Scholar 

  30. Odorizzi M, Max JP, Tankosic P, Burlet C, Burlet A . Dietary preferences of Brattleboro rats correlated with an overexpression of galanin in the hypothalamus. Eur J Neurosci 1999; 11: 3005–3014.

    Article  CAS  Google Scholar 

  31. American Physiology Society. Guiding principles for research involving animals and human beings. Am J Physiol Regul Integr Comp Physiol 2002; 283: R281–R283.

  32. Eckel RH, Prasad JE, Kern PA, Marshall S . Insulin regulation of lipoprotein lipase in cultured isolated rat adipocytes. Endocrinology 1984; 114: 1665–1671.

    Article  CAS  Google Scholar 

  33. Gayles EC, Pagliassotti MJ, Prach PA, Koppenhafer TA, Hill JO . Contribution of energy intake and tissue enzymatic profile to body weight gain in high-fat-fed rats. Am J Physiol 1997; 272: R188–R194.

    CAS  PubMed  Google Scholar 

  34. Paxinos G, Watson C . The rat brain in stereotaxic coordinates 2nd edn Academic Press: Sydney; 1986.

    Google Scholar 

  35. Wortley KE, Chang GQ, Davydova Z, Leibowitz SF . Peptides that regulate food intake: orexin gene expression is increased during states of hypertriglyceridemia. Am J Physiol Regul Integr Comp Physiol 2003; 284: R1454–R1465.

    Article  CAS  Google Scholar 

  36. Boivin A, Deshaies Y . Contribution of hyperinsulinemia to modulation of lipoprotein lipase activity in the obese Zucker rat. Metabolism 2000; 49: 134–140.

    Article  CAS  Google Scholar 

  37. Pujol A, Lefaucheur L, Ecolan P, Picon L, Penicaud L . Fiber type composition and enzyme activities of muscles in two models of obese rats. Comp Biochem Physiol B 1993; 106: 269–272.

    Article  CAS  Google Scholar 

  38. Malendowicz LK, Tortorella C, Nowak KW, Nussdorfer GG, Hochol A, Majchrzak M . Leptin prolonged administration inhibits the growth and glucocorticoid secretion of rat adrenal cortex. Endocr Res 2000; 26: 141–152.

    Article  CAS  Google Scholar 

  39. Matthys LA, Widmaier EP . Fatty acids inhibit adrenocorticotropin-induced adrenal steroidogenesis. Horm Metab Res 1998; 30: 80–83.

    Article  CAS  Google Scholar 

  40. Koyama K, Chen G, Lee Y, Unger RH . Tissue triglycerides, insulin resistance, and insulin production: implications for hyperinsulinemia of obesity. Am J Physiol 1997; 273: E708–E713.

    CAS  PubMed  Google Scholar 

  41. Bessesen DH, Rupp CL, Eckel RH . Dietary fat is shunted away from oxidation, toward storage in obese Zucker rats. Obes Res 1995; 3: 179–189.

    Article  CAS  Google Scholar 

  42. Pagliassotti MJ, Horton TJ, Gayles EC, Koppenhafer TA, Rosenzweig TD, Hill JO . Reduced insulin suppression of glucose appearance is related to susceptibility to dietary obesity in rats. Am J Physiol 1997; 272: R1264–R1270.

    CAS  PubMed  Google Scholar 

  43. Knobler H, Weiss Y, Peled M, Groner Y . Impaired glucose-induced insulin response in transgenic mice overexpressing the L-phosphofructokinase gene. Diabetes 1997; 46: 1414–1418.

    Article  CAS  Google Scholar 

  44. Wang J, Akabayashi A, Yu HJ, Dourmashkin J, Silva I, Lighter J, Leibowitz SF . Hypothalamic galanin: control by signals of fat metabolism. Brain Res 1998; 804: 7–20.

    Article  CAS  Google Scholar 

  45. Gorbatyuk O, Hokfelt T . Effect of inhibition of glucose and fat metabolism on galanin-R1 receptor mRNA levels in the rat hypothalamic paraventricular and supraoptic nuclei. Neuroreport 1998; 9: 3565–3569.

    Article  CAS  Google Scholar 

  46. Koegler FH, Ritter S . Feeding induced by pharmacological blockade of fatty acid metabolism is selectively attenuated by hindbrain injections of the galanin receptor antagonist, M40. Obes Res 1996; 4: 329–336.

    Article  CAS  Google Scholar 

  47. Chang GQ, Karatayev O, Davydova Z, Leibowitz SF . Circulating triglycerides impact on orexigenic peptides and neuronal activity in hypothalamus. Endocrinology 2004; 145: 3904–3912.

    Article  CAS  Google Scholar 

  48. Boivin A, Deshaies Y . Dietary rat models in which the development of hypertriglyceridemia and that of insulin resistance are dissociated. Metabolism 1995; 44: 1540–1547.

    Article  CAS  Google Scholar 

  49. Bhathena SJ, Aparicio P, Revett K, Voyles N, Recant L . Effect of dietary carbohydrates on glucagon and insulin receptors in genetically obese female Zucker rats. J Nutr 1987; 117: 1291–1297.

    Article  CAS  Google Scholar 

  50. Pagliassotti MJ, Prach PA, Koppenhafer TA, Pan DA . Changes in insulin action, triglycerides, and lipid composition during sucrose feeding in rats. Am J Physiol 1996; 271: R1319–R1326.

    CAS  PubMed  Google Scholar 

  51. Kyrkouli SE, Stanley BG, Leibowitz SF . Galanin: stimulation of feeding induced by medial hypothalamic injection of this novel peptide. Eur J Pharmacol 1986; 122: 159–160.

    Article  CAS  Google Scholar 

  52. Koegler FH, York DA, Bray GA . The effects on feeding of galanin and M40 when injected into the nucleus of the solitary tract, the lateral parabrachial nucleus, and the third ventricle. Physiol Behav 1999; 67: 259–267.

    Article  CAS  Google Scholar 

  53. Lin L, York DA, Bray GA . Comparison of Osborne-Mendel and S5B/PL strains of rat: central effects of galanin, NPY, beta-casomorphin and CRH on intake of high-fat and low-fat diets. Obes Res 1996; 4: 117–124.

    Article  CAS  Google Scholar 

  54. Menendez JA, Atrens DM, Leibowitz SF . Metabolic effects of galanin injections into the paraventricular nucleus of the hypothalamus. Peptides 1992; 13: 323–327.

    Article  CAS  Google Scholar 

  55. Nagase H, Nakajima A, Sekihara H, York DA, Bray GA . Regulation of feeding behavior, gastric emptying, and sympathetic nerve activity to interscapular brown adipose tissue by galanin and enterostatin: the involvement of vagal-central nervous system interactions. J Gastroenterol 2002; 37: 118–127.

    Article  CAS  Google Scholar 

  56. Yun R, Dourmashkin JT, Hill J, Gayles EC, Fried SK, Leibowitz SF . PVN galanin increases fat storage and promotes obesity by causing muscle to utilize carbohydrate more than fat. Peptides 2005; in press.

  57. Barton C, Lin L, York DA, Bray GA . Differential effects of enterostatin, galanin and opioids on high-fat diet consumption. Brain Res 1995; 702: 55–60.

    Article  CAS  Google Scholar 

  58. Smith BK, York DA, Bray GA . Chronic cerebroventricular galanin does not induce sustained hyperphagia or obesity. Peptides 1994; 15: 1267–1272.

    Article  CAS  Google Scholar 

  59. Akabayashi A, Koenig JI, Watanabe Y, Alexander JT, Leibowitz SF . Galanin-containing neurons in the paraventricular nucleus: a neurochemical marker for fat ingestion and body weight gain. Proc Natl Acad Sci USA 1994; 91: 10375–10379.

    Article  CAS  Google Scholar 

  60. Cheung CC, Hohmann JG, Clifton DK, Steiner RA . Distribution of galanin messenger RNA-expressing cells in murine brain and their regulation by leptin in regions of the hypothalamus. Neuroscience 2001; 103: 423–432.

    Article  CAS  Google Scholar 

  61. Tang C, Akabayashi A, Manitiu A, Leibowitz SF . Hypothalamic galanin gene expression and peptide levels in relation to circulating insulin: possible role in energy balance. Neuroendocrinology 1997; 65: 265–275.

    Article  CAS  Google Scholar 

  62. Hedlund PB, Koenig JI, Fuxe K . Adrenalectomy alters discrete galanin mRNA levels in the hypothalamus and mesencephalon of the rat. Neurosci Lett 1994; 170: 77–82.

    Article  CAS  Google Scholar 

  63. Akabayashi A, Watanabe Y, Gabriel SM, Chae HJ, Leibowitz SF . Hypothalamic galanin-like immunoreactivity and its gene expression in relation to circulating corticosterone. Brain Res Mol Brain Res 1994; 25: 305–312.

    Article  CAS  Google Scholar 

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Acknowledgements

We are grateful to Ms Kate Sepiashvili, Patricia Pamy, and Olga Karatayev for their help in the preparation of this manuscript. This research was supported by a USPHS Grant, MH43422.

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Correspondence to S F Leibowitz.

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Dourmashkin, J., Chang, GQ., Gayles, E. et al. Different forms of obesity as a function of diet composition. Int J Obes 29, 1368–1378 (2005). https://doi.org/10.1038/sj.ijo.0803017

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