Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Original Article
  • Published:

Peripheral neuropeptide Y Y1 receptors regulate lipid oxidation and fat accretion

International Journal of Obesity volume 34, pages 357–373 (2010)Cite this article

Abstract

Objective:

Neuropeptide Y and its Y receptors are important players in the regulation of energy homeostasis. However, while their functions in feeding regulation are well recognized, functions in other critical aspects of energy homeostasis are largely unknown. To investigate the function of Y1 receptors in the regulation of energy homeostasis, we examined energy expenditure, physical activity, body composition, oxidative fuel selection and mitochondrial oxidative capacity in germline Y1−/− mice as well as in a conditional Y1-receptor-knockdown model in which Y1 receptors were knocked down in peripheral tissues of adult mice.

Results:

Germline Y1−/− mice of both genders not only exhibit a decreased respiratory exchange ratio, indicative of increased lipid oxidation, but interestingly also develop late-onset obesity. However, the increased lipid oxidation is a primary effect of Y1 deletion rather than secondary to increased adiposity, as young Y1−/− mice are lean and show the same effect. The mechanism behind this is likely because of increased liver and muscle protein levels of carnitine palmitoyltransferase-1 (CPT-1) and maximal activity of key enzymes involved in β-oxidation; β-hydroxyacyl CoA dehydrogenase (βHAD) and medium-chain acyl-CoA dehydrogenase (MCAD), leading to increased mitochondrial capacity for fatty acid transport and oxidation. These effects are controlled by peripheral Y1-receptor signalling, as adult-onset conditional Y1 knockdown in peripheral tissues also leads to increased lipid oxidation, liver CPT-1 levels and βHAD activity. Importantly, these mice are resistant to diet-induced obesity.

Conclusions:

This work shows the primary function of peripheral Y1 receptors in the regulation of oxidative fuel selection and adiposity, opening up new avenues for anti-obesity treatments by targeting energy utilization in peripheral tissues rather than suppressing appetite by central effects.

This is a preview of subscription content, access via your institution

Access options

Buy this article

  • Purchase on Springer Link
  • Instant access to full article PDF
Buy now

Prices may be subject to local taxes which are calculated during checkout

Figure 1
Figure 2
Figure 3
Figure 4

Similar content being viewed by others

References

  1. Raposinho PD, Pierroz DD, Broqua P, White RB, Pedrazzini T, Aubert ML . Chronic administration of neuropeptide Y into the lateral ventricle of C57BL/6J male mice produces an obesity syndrome including hyperphagia, hyperleptinemia, insulin resistance, and hypogonadism. Mol Cell Endocrinol 2001; 185: 195–204.

    CAS  PubMed  Google Scholar 

  2. Sainsbury A, Rohner-Jeanrenaud F, Cusin I, Zakrzewska KE, Halban PA, Gaillard RC et al. Chronic central neuropeptide Y infusion in normal rats: status of the hypothalamo-pituitary-adrenal axis, and vagal mediation of hyperinsulinaemia. Diabetologia 1997; 40: 1269–1277.

    CAS  PubMed  Google Scholar 

  3. Lin EJ, Sainsbury A, Lee NJ, Boey D, Couzens M, Enriquez R et al. Combined deletion of Y1, Y2 and Y4 receptors prevents hypothalamic NPY overexpression-induced hyperinsulinemia despite persistence of hyperphagia and obesity. Endocrinology 2006; 147: 5094–5101.

    CAS  PubMed  Google Scholar 

  4. Kotz CM, Briggs JE, Grace MK, Levine AS, Billington CJ . Divergence of the feeding and thermogenic pathways influenced by NPY in the hypothalamic PVN of the rat. Am J Physiol 1998; 275: R471–R477.

    CAS  PubMed  Google Scholar 

  5. Hwa JJ, Witten MB, Williams P, Ghibaudi L, Gao J, Salisbury BG et al. Activation of the NPY Y5 receptor regulates both feeding and energy expenditure. Am J Physiol 1999; 277: R1428–R1434.

    CAS  PubMed  Google Scholar 

  6. Stanley BG, Kyrkouli SE, Lampert S, Leibowitz SF . Neuropeptide Y chronically injected into the hypothalamus: a powerful neurochemical inducer of hyperphagia and obesity. Peptides 1986; 7: 1189–1192.

    CAS  PubMed  Google Scholar 

  7. Billington CJ, Briggs JE, Grace M, Levine AS . Effects of intracerebroventricular injection of neuropeptide Y on energy metabolism. Am J Physiol 1991; 260: R321–R327.

    CAS  PubMed  Google Scholar 

  8. Billington CJ, Briggs JE, Harker S, Grace M, Levine AS . Neuropeptide Y in hypothalamic paraventricular nucleus: a center coordinating energy metabolism. Am J Physiol 1994; 266: R1765–R1770.

    CAS  PubMed  Google Scholar 

  9. Szreder Z, Hori T, Kaizuka Y . Thermoregulatory effect of intracerebral injections of neuropeptide Y in rats at different environmental temperatures. Gen Pharmacol 1994; 25: 85–91.

    CAS  PubMed  Google Scholar 

  10. Currie PJ, Coscina DV . Dissociated feeding and hypothermic effects of neuropeptide Y in the paraventricular and perifornical hypothalamus. Peptides 1995; 16: 599–604.

    CAS  PubMed  Google Scholar 

  11. Zarjevski N, Cusin I, Vettor R, Rohner-Jeanrenaud F, Jeanrenaud B . Intracerebroventricular administration of neuropeptide Y to normal rats has divergent effects on glucose utilization by adipose tissue and skeletal muscle. Diabetes 1994; 43: 764–769.

    CAS  PubMed  Google Scholar 

  12. Zarjevski N, Cusin I, Vettor R, Rohner-Jeanrenaud F, Jeanrenaud B . Chronic intracerebroventricular neuropeptide-Y administration to normal rats mimics hormonal and metabolic changes of obesity. Endocrinology 1993; 133: 1753–1758.

    CAS  PubMed  Google Scholar 

  13. Menendez JA, McGregor IS, Healey PA, Atrens DM, Leibowitz SF . Metabolic effects of neuropeptide Y injections into the paraventricular nucleus of the hypothalamus. Brain Res 1990; 516: 8–14.

    CAS  PubMed  Google Scholar 

  14. Currie PJ, Coscina DV, Bishop C, Coiro CD, Koob GF, Rivier J et al. Hypothalamic paraventricular nucleus injections of urocortin alter food intake and respiratory quotient. Brain Res 2001; 916: 222–228.

    CAS  PubMed  Google Scholar 

  15. Henry M, Ghibaudi L, Gao J, Hwa JJ . Energy metabolic profile of mice after chronic activation of central NPY Y1, Y2, or Y5 receptors. Obes Res 2005; 13: 36–47.

    CAS  PubMed  Google Scholar 

  16. Blomqvist AG, Herzog H . Y-receptor subtypes—how many more? Trends Neurosci 1997; 20: 294–298.

    CAS  PubMed  Google Scholar 

  17. Kanatani A, Hata M, Mashiko S, Ishihara A, Okamoto O, Haga Y et al. A typical Y1 receptor regulates feeding behaviors: effects of a potent and selective Y1 antagonist, J-115814. Mol Pharmacol 2001; 59: 501–505.

    CAS  PubMed  Google Scholar 

  18. Kanatani A, Kanno T, Ishihara A, Hata M, Sakuraba A, Tanaka T et al. The novel neuropeptide Y Y(1) receptor antagonist J-104870: a potent feeding suppressant with oral bioavailability. Biochem Biophys Res Commun 1999; 266: 88–91.

    CAS  PubMed  Google Scholar 

  19. Haynes AC, Arch JR, Wilson S, McClue S, Buckingham RE . Characterisation of the neuropeptide Y receptor that mediates feeding in the rat: a role for the Y5 receptor? Regul Pept 1998; 75–76: 355–361.

    PubMed  Google Scholar 

  20. Antal-Zimanyi I, Bruce MA, Leboulluec KL, Iben LG, Mattson GK, McGovern RT et al. Pharmacological characterization and appetite suppressive properties of BMS-193885, a novel and selective neuropeptide Y(1) receptor antagonist. Eur J Pharmacol 2008; 590: 224–232.

    CAS  PubMed  Google Scholar 

  21. Mullins D, Kirby D, Hwa J, Guzzi M, Rivier J, Parker E . Identification of potent and selective neuropeptide Y Y(1) receptor agonists with orexigenic activity in vivo. Mol Pharmacol 2001; 60: 534–540.

    CAS  PubMed  Google Scholar 

  22. Sainsbury A, Bergen HT, Boey D, Bamming D, Cooney GJ, Lin S et al. Y2Y4 receptor double knockout protects against obesity due to a high-fat diet or Y1 receptor deficiency in mice. Diabetes 2006; 55: 19–26.

    CAS  PubMed  Google Scholar 

  23. Baldock PA, Allison SJ, Lundberg P, Lee NJ, Slack K, Lin EJ et al. Novel role of Y1 receptors in the coordinated regulation of bone and energy homeostasis. J Biol Chem 2007; 282: 19092–19102.

    CAS  PubMed  Google Scholar 

  24. Pedrazzini T, Seydoux J, Kunstner P, Aubert JF, Grouzmann E, Beermann F et al. Cardiovascular response, feeding behavior and locomotor activity in mice lacking the NPY Y1 receptor. Nat Med 1998; 4: 722–726.

    CAS  PubMed  Google Scholar 

  25. Kushi A, Sasai H, Koizumi H, Takeda N, Yokoyama M, Nakamura M . Obesity and mild hyperinsulinemia found in neuropeptide Y-Y1 receptor-deficient mice. Proc Natl Acad Sci USA 1998; 95: 15659–15664.

    CAS  PubMed  PubMed Central  Google Scholar 

  26. Leibel RL, Rosenbaum M, Hirsch J . Changes in energy expenditure resulting from altered body weight. N Engl J Med 1995; 332: 621–628.

    CAS  PubMed  Google Scholar 

  27. Berglund MM, Hipskind PA, Gehlert DR . Recent developments in our understanding of the physiological role of PP-fold peptide receptor subtypes. Exp Biol Med (Maywood) 2003; 228: 217–244.

    CAS  Google Scholar 

  28. Goumain M, Voisin T, Lorinet AM, Laburthe M . Identification and distribution of mRNA encoding the Y1, Y2, Y4, and Y5 receptors for peptides of the PP-fold family in the rat intestine and colon. Biochem Biophys Res Commun 1998; 247: 52–56.

    CAS  PubMed  Google Scholar 

  29. Yang K, Guan H, Arany E, Hill DJ, Cao X . Neuropeptide Y is produced in visceral adipose tissue and promotes proliferation of adipocyte precursor cells via the Y1 receptor. FASEB J 2008; 7: 7.

    Google Scholar 

  30. Serradeil-Le Gal C, Lafontan M, Raufaste D, Marchand J, Pouzet B, Casellas P et al. Characterization of NPY receptors controlling lipolysis and leptin secretion in human adipocytes. FEBS Lett 2000; 475: 150–156.

    CAS  PubMed  Google Scholar 

  31. Kuo LE, Kitlinska JB, Tilan JU, Li L, Baker SB, Johnson MD et al. Neuropeptide Y acts directly in the periphery on fat tissue and mediates stress-induced obesity and metabolic syndrome. Nat Med 2007; 13: 803–811.

    CAS  PubMed  Google Scholar 

  32. Dark J, Pelz KM . NPY Y1 receptor antagonist prevents NPY-induced torpor-like hypothermia in cold-acclimated Siberian hamsters. Am J Physiol Regul Integr Comp Physiol 2008; 294: R236–R245.

    CAS  PubMed  Google Scholar 

  33. Dark J, Pelz KM . ICV NPY Y1 receptor agonist but not Y5 agonist induces torpor-like hypothermia in cold-acclimated Siberian hamsters. Am J Physiol Regul Integr Comp Physiol 2007; 292: R2299–R2311.

    PubMed  Google Scholar 

  34. Trivedi PG, Yu H, Trumbauer M, Chen H, Van der Ploeg LH, Guan X . Differential regulation of neuropeptide Y receptors in the brains of NPY knock-out mice. Peptides 2001; 22: 395–403.

    CAS  PubMed  Google Scholar 

  35. Wittmann W, Loacker S, Kapeller I, Herzog H, Schwarzer C . Y1-receptors regulate the expression of Y2-receptors in distinct mouse forebrain areas. Neuroscience 2005; 136: 241–250.

    CAS  PubMed  Google Scholar 

  36. Lin S, Boey D, Couzens M, Lee N, Sainsbury A, Herzog H . Compensatory changes in [125I]-PYY binding in Y receptor knockout mice suggest the potential existence of further Y receptor(s). Neuropeptides 2005; 39: 21–28.

    CAS  PubMed  Google Scholar 

  37. Marsh DJ, Hollopeter G, Kafer KE, Palmiter RD . Role of the Y5 neuropeptide Y receptor in feeding and obesity. Nat Med 1998; 4: 718–721.

    CAS  PubMed  Google Scholar 

  38. Howell OW, Scharfman HE, Herzog H, Sundstrom LE, Beck-Sickinger A, Gray WP . Neuropeptide Y is neuroproliferative for post-natal hippocampal precursor cells. J Neurochem 2003; 86: 646–659.

    CAS  PubMed  Google Scholar 

  39. Kuhn R, Schwenk F, Aguet M, Rajewsky K . Inducible gene targeting in mice. Science 1995; 269: 1427–1429.

    CAS  PubMed  Google Scholar 

  40. Ferrannini E . The theoretical bases of indirect calorimetry: a review. Metabolism 1988; 37: 287–301.

    CAS  PubMed  Google Scholar 

  41. Frayn KN . Calculation of substrate oxidation rates in vivo from gaseous exchange. J Appl Physiol 1983; 55: 628–634.

    CAS  PubMed  Google Scholar 

  42. McLean JA, Tobin G . Animal and Human Calorimetry. Cambridge University Press: New York, 1987. pp 352.

    Google Scholar 

  43. Turner N, Bruce CR, Beale SM, Hoehn KL, So T, Rolph MS et al. Excess lipid availability increases mitochondrial fatty acid oxidative capacity in muscle: evidence against a role for reduced fatty acid oxidation in lipid-induced insulin resistance in rodents. Diabetes 2007; 56: 2085–2092.

    CAS  PubMed  Google Scholar 

  44. Molero JC, Waring SG, Cooper A, Turner N, Laybutt R, Cooney GJ et al. Casitas b-lineage lymphoma-deficient mice are protected against high-fat diet-induced obesity and insulin resistance. Diabetes 2006; 55: 708–715.

    CAS  PubMed  Google Scholar 

  45. Djouadi F, Riveau B, Merlet-Benichou C, Bastin J . Tissue-specific regulation of medium-chain acyl-CoA dehydrogenase gene by thyroid hormones in the developing rat. Biochem J 1997; 324 (Pt 1): 289–294.

    CAS  PubMed  PubMed Central  Google Scholar 

  46. Franklin KBJ, Paxinos G . The mouse brain in stereotaxic coordinates. Academic Press: California 1997, pp 47–48.

  47. Saggerson ED, Carpenter CA . Carnitine palmitoyltransferase and carnitine octanoyltransferase activities in liver, kidney cortex, adipocyte, lactating mammary gland, skeletal muscle and heart. FEBS Lett 1981; 129: 229–232.

    CAS  PubMed  Google Scholar 

  48. McGarry JD, Mills SE, Long CS, Foster DW . Observations on the affinity for carnitine, and malonyl-CoA sensitivity, of carnitine palmitoyltransferase I in animal and human tissues. Demonstration of the presence of malonyl-CoA in non-hepatic tissues of the rat. Biochem J 1983; 214: 21–28.

    CAS  PubMed  PubMed Central  Google Scholar 

  49. Lin J, Handschin C, Spiegelman BM . Metabolic control through the PGC-1 family of transcription coactivators. Cell Metab 2005; 1: 361–370.

    PubMed  Google Scholar 

  50. Daniels AJ, Matthews JE, Slepetis RJ, Jansen M, Viveros OH, Tadepalli A et al. High-affinity neuropeptide Y receptor antagonists. Proc Natl Acad Sci USA 1995; 92: 9067–9071.

    CAS  PubMed  PubMed Central  Google Scholar 

  51. Fam BC, Morris MJ, Hansen MJ, Andrikopoulos S, Proietto J, Thorburn AW . Modulation of central leptin sensitivity and energy balance in a rat model of diet-induced obesity. Diabetes Obes Metab 2007; 9: 840–852.

    CAS  PubMed  Google Scholar 

  52. Iossa S, Mollica MP, Lionetti L, Crescenzo R, Botta M, Liverini G . Skeletal muscle oxidative capacity in rats fed high-fat diet. Int J Obes Relat Metab Disord 2002; 26: 65–72.

    CAS  PubMed  Google Scholar 

  53. Levine JA, Eberhardt NL, Jensen MD . Role of nonexercise activity thermogenesis in resistance to fat gain in humans. Science 1999; 283: 212–214.

    CAS  PubMed  Google Scholar 

  54. Tran TT, Yamamoto Y, Gesta S, Kahn CR . Beneficial effects of subcutaneous fat transplantation on metabolism. Cell Metab 2008; 7: 410–420.

    CAS  PubMed  PubMed Central  Google Scholar 

  55. Hocking SL, Chisholm DJ, James DE . Studies of regional adipose transplantation reveal a unique and beneficial interaction between subcutaneous adipose tissue and the intra-abdominal compartment. Diabetologia 2008; 51: 900–902.

    CAS  PubMed  Google Scholar 

  56. Ravussin E, Lillioja S, Anderson TE, Christin L, Bogardus C . Determinants of 24-hour energy expenditure in man. Methods and results using a respiratory chamber. J Clin Invest 1986; 78: 1568–1578.

    CAS  PubMed  PubMed Central  Google Scholar 

  57. Vogels N, Westerterp-Plantenga MS . Successful long-term weight maintenance: a 2-year follow-up. Obesity (Silver Spring) 2007; 15: 1258–1266.

    Google Scholar 

  58. Vogels N, Diepvens K, Westerterp-Plantenga MS . Predictors of long-term weight maintenance. Obes Res 2005; 13: 2162–2168.

    PubMed  Google Scholar 

  59. Illner K, Brinkmann G, Heller M, Bosy-Westphal A, Muller MJ . Metabolically active components of fat free mass and resting energy expenditure in nonobese adults. Am J Physiol Endocrinol Metab 2000; 278: E308–E315.

    CAS  PubMed  Google Scholar 

  60. Muller MJ . Hepatic energy and substrate metabolism: a possible metabolic basis for early nutritional support in cirrhotic patients. Nutrition 1998; 14: 30–38.

    CAS  PubMed  Google Scholar 

  61. Kelley DE, Reilly JP, Veneman T, Mandarino LJ . Effects of insulin on skeletal muscle glucose storage, oxidation, and glycolysis in humans. Am J Physiol 1990; 258: E923–E929.

    CAS  PubMed  Google Scholar 

  62. Rasmussen BB, Wolfe RR . Regulation of fatty acid oxidation in skeletal muscle. Annu Rev Nutr 1999; 19: 463–484.

    CAS  PubMed  Google Scholar 

  63. Bruce CR, Brolin C, Turner N, Cleasby ME, Van der Leij FR, Cooney GJ et al. Overexpression of carnitine palmitoyltransferase I in skeletal muscle in vivo increases fatty acid oxidation and reduces triacylglycerol esterification. Am J Physiol Endocrinol Metab 2007; 292: E1231–E1237.

    CAS  PubMed  Google Scholar 

  64. Tanaka K, Yokota I, Coates PM, Strauss AW, Kelly DP, Zhang Z et al. Mutations in the medium chain acyl-CoA dehydrogenase (MCAD) gene. Hum Mutat 1992; 1: 271–279.

    CAS  PubMed  Google Scholar 

  65. Jequier E . Leptin signaling, adiposity, and energy balance. Ann N Y Acad Sci 2002; 967: 379–388.

    CAS  PubMed  Google Scholar 

  66. Pedrazzini T . Importance of NPY Y1 receptor-mediated pathways: assessment using NPY Y1 receptor knockouts. Neuropeptides 2004; 38: 267–275.

    CAS  PubMed  Google Scholar 

  67. Chelikani PK, Haver AC, Reeve Jr JR, Keire DA, Reidelberger RD . Daily, intermittent intravenous infusion of peptide YY(3–36) reduces daily food intake and adiposity in rats. Am J Physiol Regul Integr Comp Physiol 2006; 290: R298–R305.

    CAS  PubMed  Google Scholar 

  68. Pralong FP, Gonzales C, Voirol MJ, Palmiter RD, Brunner HR, Gaillard RC et al. The neuropeptide Y Y1 receptor regulates leptin-mediated control of energy homeostasis and reproductive functions. FASEB J 2002; 16: 712–714.

    CAS  PubMed  Google Scholar 

  69. Gonzales C, Voirol MJ, Giacomini M, Gaillard RC, Pedrazzini T, Pralong FP . The neuropeptide Y Y1 receptor mediates NPY-induced inhibition of the gonadotrope axis under poor metabolic conditions. FASEB J 2004; 18: 137–139.

    CAS  PubMed  Google Scholar 

  70. D′Eon TM, Souza SC, Aronovitz M, Obin MS, Fried SK, Greenberg AS . Estrogen regulation of adiposity and fuel partitioning. Evidence of genomic and non-genomic regulation of lipogenic and oxidative pathways. J Biol Chem 2005; 280: 35983–35991.

    PubMed  Google Scholar 

  71. Ogawa S, Chan J, Gustafsson JA, Korach KS, Pfaff DW . Estrogen increases locomotor activity in mice through estrogen receptor alpha: specificity for the type of activity. Endocrinology 2003; 144: 230–239.

    CAS  PubMed  Google Scholar 

  72. Mattiasson I, Rendell M, Tornquist C, Jeppsson S, Hulthen UL . Effects of estrogen replacement therapy on abdominal fat compartments as related to glucose and lipid metabolism in early postmenopausal women. Horm Metab Res 2002; 34: 583–588.

    CAS  PubMed  Google Scholar 

  73. Mudali S, Dobs AS . Effects of testosterone on body composition of the aging male. Mech Ageing Dev 2004; 125: 297–304.

    CAS  PubMed  Google Scholar 

  74. Poehlman ET . Menopause, energy expenditure, and body composition. Acta Obstet Gynecol Scand 2002; 81: 603–611.

    PubMed  Google Scholar 

  75. Blouin K, Despres JP, Couillard C, Tremblay A, Prud′homme D, Bouchard C et al. Contribution of age and declining androgen levels to features of the metabolic syndrome in men. Metabolism 2005; 54: 1034–1040.

    CAS  PubMed  Google Scholar 

  76. Karl T, Burne TH, Herzog H . Effect of Y1 receptor deficiency on motor activity, exploration, and anxiety. Behav Brain Res 2006; 167: 87–93.

    CAS  PubMed  Google Scholar 

  77. Bartness TJ, Song CK . Thematic review series: adipocyte biology. Sympathetic and sensory innervation of white adipose tissue. J Lipid Res 2007; 48: 1655–1672.

    CAS  PubMed  Google Scholar 

  78. Carey GB . Mechanisms regulating adipocyte lipolysis. Adv Exp Med Biol 1998; 441: 157–170.

    CAS  PubMed  Google Scholar 

  79. Egawa M, Yoshimatsu H, Bray GA . Neuropeptide Y suppresses sympathetic activity to interscapular brown adipose tissue in rats. Am J Physiol 1991; 260: R328–R334.

    CAS  PubMed  Google Scholar 

  80. Michalkiewicz M, Knestaut KM, Bytchkova EY, Michalkiewicz T . Hypotension and reduced catecholamines in neuropeptide Y transgenic rats. Hypertension 2003; 41: 1056–1062.

    CAS  PubMed  Google Scholar 

  81. Yang SN, Finnman UB, Fuxe K . The non-peptide neuropeptide Y Y1 receptor antagonist BIBP3226 blocks the [Leu31,Pro34]neuropeptide Y-induced modulation of alpha 2-adrenoceptors in the nucleus tractus solitarii of the rat. Neuroreport 1996; 7: 2701–2705.

    CAS  PubMed  Google Scholar 

  82. Glass MJ, Chan J, Pickel VM . Ultrastructural localization of neuropeptide Y Y1 receptors in the rat medial nucleus tractus solitarius: relationships with neuropeptide Y or catecholamine neurons. J Neurosci Res 2002; 67: 753–765.

    CAS  PubMed  Google Scholar 

  83. Bowers RR, Festuccia WT, Song CK, Shi H, Migliorini RH, Bartness TJ . Sympathetic innervation of white adipose tissue and its regulation of fat cell number. Am J Physiol Regul Integr Comp Physiol 2004; 286: R1167–R1175.

    CAS  PubMed  Google Scholar 

  84. Labelle M, Boulanger Y, Fournier A, St Pierre S, Savard R . Tissue-specific regulation of fat cell lipolysis by NPY in 6-OHDA-treated rats. Peptides 1997; 18: 801–808.

    CAS  PubMed  Google Scholar 

  85. Bradley RL, Mansfield JP, Maratos-Flier E . Neuropeptides, including neuropeptide Y and melanocortins, mediate lipolysis in murine adipocytes. Obes Res 2005; 13: 653–661.

    CAS  PubMed  Google Scholar 

  86. Valet P, Berlan M, Beauville M, Crampes F, Montastruc JL, Lafontan M . Neuropeptide Y and peptide YY inhibit lipolysis in human and dog fat cells through a pertussis toxin-sensitive G protein. J Clin Invest 1990; 85: 291–295.

    CAS  PubMed  PubMed Central  Google Scholar 

  87. Castan I, Valet P, Quideau N, Voisin T, Ambid L, Laburthe M et al. Antilipolytic effects of alpha 2-adrenergic agonists, neuropeptide Y, adenosine, and PGE1 in mammal adipocytes. Am J Physiol 1994; 266: R1141–R1147.

    CAS  PubMed  Google Scholar 

  88. Phillips JK, McLean AJ, Hill CE . Receptors involved in nerve-mediated vasoconstriction in small arteries of the rat hepatic mesentery. Br J Pharmacol 1998; 124: 1403–1412.

    CAS  PubMed  PubMed Central  Google Scholar 

  89. Goehler LE, Sternini C . Neuropeptide Y immunoreactivity in the mammalian liver: pattern of innervation and coexistence with tyrosine hydroxylase immunoreactivity. Cell Tissue Res 1991; 265: 287–295.

    CAS  PubMed  Google Scholar 

  90. Taborsky Jr GJ, Beltramini LM, Brown M, Veith RC, Kowalyk S . Canine liver releases neuropeptide Y during sympathetic nerve stimulation. Am J Physiol 1994; 266: E804–E812.

    CAS  PubMed  Google Scholar 

  91. Padwal RS, Majumdar SR . Drug treatments for obesity: orlistat, sibutramine, and rimonabant. Lancet 2007; 369: 71–77.

    CAS  PubMed  Google Scholar 

Download references

Acknowledgements

We are grateful to Associate Professor Gregory J Cooney of the Garvan Institute for help with set-up and use of the Columbus Instruments Laboratory Animal Monitoring System. We thank the staff of the Garvan Institute Biological Testing Facility for facilitation of these experiments. We appreciate Nuala M Byrne, PhD, Institute of Health and Biomedical Innovation, Queensland University of Technology, Australia, for scientific discussion of the results. The expert administrative help of Gemma Macdonald and Samantha Lee of the Garvan Institute in the preparation and submission of this manuscript is gratefully acknowledged. This research was supported by a grant from the National Health and Medical Research Council (NHMRC) of Australia, a Career Development award to NT and NHMRC Fellowships to HH and AS.

Author information

Author notes

  1. H Herzog and A Sainsbury: These two authors contributed equally to this work.

Authors and Affiliations

  1. Neuroscience Research Program, Garvan Institute of Medical Research, Darlinghurst, Sydney, New South Wales, Australia

    L Zhang, L Macia, S J Riepler, A D Nguyen, S Lin, N J Lee, Y C Shi, E Yulyaningsih, K Slack, H Herzog & A Sainsbury

  2. Diabetes and Obesity Program, Garvan Institute of Medical Research, Darlinghurst, Sydney, New South Wales, Australia

    N Turner

  3. St. Vincent's Hospital Clinical School, University of New South Wales, Sydney, New South Wales, Australia

    N Turner & P A Baldock

  4. Bone and Mineral Research Program, Garvan Institute of Medical Research, Darlinghurst, Sydney, New South Wales, Australia

    R F Enriquez

  5. Faculty of Medicine, University of New South Wales, Sydney, New South Wales, Australia

    H Herzog

  6. School of Medical Sciences, University of New South Wales, Sydney, New South Wales, Australia

    A Sainsbury

Authors
  1. L Zhang
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. L Macia
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. N Turner
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. R F Enriquez
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. S J Riepler
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. A D Nguyen
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. S Lin
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. N J Lee
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Y C Shi
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. E Yulyaningsih
    View author publications

    You can also search for this author in PubMed Google Scholar

  11. K Slack
    View author publications

    You can also search for this author in PubMed Google Scholar

  12. P A Baldock
    View author publications

    You can also search for this author in PubMed Google Scholar

  13. H Herzog
    View author publications

    You can also search for this author in PubMed Google Scholar

  14. A Sainsbury
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to H Herzog.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Zhang, L., Macia, L., Turner, N. et al. Peripheral neuropeptide Y Y1 receptors regulate lipid oxidation and fat accretion. Int J Obes 34, 357–373 (2010). https://doi.org/10.1038/ijo.2009.232

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/ijo.2009.232

Keywords

This article is cited by

Search

Advanced search

Quick links