51
Views
3
CrossRef citations to date
0
Altmetric
Review

Current trends in targeting the hormonal regulation of appetite and energy balance to treat obesity

, , &
Pages 765-783 | Published online: 10 Jan 2014

References

  • James WP. The epidemiology of obesity: the size of the problem. J. Intern. Med.263(4), 336–352 (2008).
  • WHO. Reducing Risks, Promoting Healthy Life. In: The World Health Report 2002. World Health Organisation, Geneva, Switzerland (2002).
  • Daniels J. Obesity: America’s epidemic. Am. J. Nurs.106(1), 40–49 (2006).
  • Dehghan M, Akhtar-Danesh N, Merchant AT. Childhood obesity, prevalence and prevention. Nutr. J.4, 24 (2005).
  • Lobstein T, Baur L, Uauy R. Obesity in children and young people: a crisis in public health. Obes. Rev. Suppl.5(1), 4–104 (2004).
  • Kopelman P. Health risks associated with overweight and obesity. Obes. Rev.8(Suppl. 1), 13–17 (2007).
  • Sturm R. The effects of obesity, smoking, and drinking on medical problems and costs. Health Affairs21(2), 245–253 (2002).
  • Sturm R. Increases in morbid obesity in the USA: 2000–2005. Public Health121(7), 492–496 (2007).
  • Miller ER 3rd, Erlinger TP, Young DR et al. Results of the diet, exercise, and weight loss intervention trial (DEW-IT). Hypertension40(5), 612–618 (2002).
  • Goldstein DJ. Beneficial health effects of modest weight loss. Int. J. Obes.16(6), 397–415 (1992).
  • Wadden TA, Butryn ML, Wilson C. Lifestyle modification for the management of obesity. Gastroenterology132(6), 2226–2238 (2007).
  • Sarwer DB, von Sydow Green A, Vetter ML, Wadden TA. Behavior therapy for obesity: where are we now? Curr. Opin. Endocrinol. Diabetes Obes.16(5), 347–352 (2009).
  • Perri M, Corsica J. Improving the maintenance of weight lost in behavioral treatment of obesity. In: Handbook of Obesity Treatment. Wadden T, Stunkard A (Eds). Guilford Press, NY, USA 357–379 (2002).
  • Buchwald H, Avidor Y, Braunwald E et al. Bariatric surgery: a systematic review and meta-analysis. JAMA292(14), 1724–1737 (2004).
  • Sjöström L, Lindroos AK, Peltonen M et al. Lifestyle, diabetes, and cardiovascular risk factors 10 years after bariatric surgery. N. Engl. J. Med.351(26), 2683–2693 (2004).
  • Maggard MA, Shugarman LR, Suttorp M et al. Meta-analysis: surgical treatment of obesity. Ann. Intern. Med.142(7), 547–559 (2005).
  • Sjöström L, Rissanen A, Andersen T et al. Randomised placebo-controlled trial of orlistat for weight loss and prevention of weight regain in obese patients. Lancet352(9123), 167–172 (1998).
  • Davidson MH, Hauptman J, DiGirolamo M et al. Weight control and risk factor reduction in obese subjects treated for 2 years with orlistat: a randomized controlled trial. JAMA281(3), 235–242 (1999).
  • James WP, Astrup A, Finer N et al. Effect of sibutramine on weight maintenance after weight loss: a randomised trial. Lancet356(Suppl.), 2119–2125 (2000).
  • Diets, drugs and surgery for weight loss. Treat. Guidel. Med. Lett.6(68), 23–28 (2008).
  • Bays HE. Current and investigational antiobesity agents and obesity therapeutic treatment targets. Obes. Res.12(8), 1197–1211 (2004).
  • Padwal RS, Majumdar SR. Drug treatments for obesity: orlistat, sibutramine, and rimonabant. Lancet369(9555), 71–77 (2007).
  • Rucker D, Padwal R, Li SK, Curioni C, Lau DC. Long term pharmacotherapy for obesity and overweight: updated meta-analysis. BMJ335(7631), 1194–1199 (2007).
  • Hofbauer KG, Nicholson JR, Boss O. The obesity epidemic: current and future pharmacological treatments. Annu. Rev. Pharmacol. Toxicol.47, 565–592 (2007).
  • Brobeck JR. Mechanism of the development of obesity in animals with hypothalamic lesions. Physiol. Rev.26, 541–559 (1946).
  • Anand BK, Brobeck JR. Hypothalamic control of food intake in rats and cats. Yale J. Biol. Med.24, 123–140 (1951).
  • Sclafani A. Neural pathways involved in the ventromedial hypothalamic lesion syndrome in the rat. J. Comp. Physiol. Psychol.77(1), 70–96 (1971).
  • Sclafani A, Kirchgessner A. The role of the medial hypothalamus in the control of food intake: an update. Feeding Behavior9, 27–66 (1986).
  • Stellar E. The physiology of motivation. Psychol. Rev.61(1), 5–22 (1954).
  • Wynne K, Stanley S, McGowan B, Bloom SR. Appetite control. J. Endocrinol.184(2), 291–318 (2005).
  • Rethelyi M. Diffusional barrier around the hypothalamic arcuate nucleus in the rat. Brain Res.307(1–2), 355–358 (1984).
  • Schwartz MW, Woods SC, Porte D Jr, Seeley RJ, Baskin DG. Central nervous system control of food intake. Nature404(6778), 661–671 (2000).
  • Badman MK, Flier JS. The gut and energy balance: visceral allies in the obesity wars. Science307(5717), 1909–1914 (2005).
  • Fan W, Boston BA, Kesterson RA, Hruby VJ, Cone RD. Role of melanocortlnergic neurons in feeding and the agouti obesity syndrome. Nature385(6612), 165–168 (1997).
  • Huszar D, Lynch CA, Fairchild-Huntress V et al. Targeted disruption of the melanocortin-4 receptor results in obesity in mice. Cell88(1), 131–141 (1997).
  • Argyropoulos G, Rankinen T, Neufeld DR et al. A polymorphism in the human agouti-related protein is associated with late-onset obesity. J. Clin. Endocrinol. Metab.87(9), 4198–4202 (2002).
  • Kristensen P, Judge ME, Thim L et al. Hypothalamic CART is a new anorectic peptide regulated by leptin. Nature393(6680), 72–76 (1998).
  • Abbott CR, Rossi M, Wren AM et al. Evidence of an orexigenic role for cocaine- and amphetamine-regulated transcript after administration into discrete hypothalamic nuclei. Endocrinology142(8), 3457–3463 (2001).
  • Shutter JR, Graham M, Kinsey AC, Scully S, Lüthy R, Stark KL. Hypothalamic expression of ART, a novel gene related to agouti, is up-regulated in obese and diabetic mutant mice. Genes Dev.11(5), 593–602 (1997).
  • Swart I, Jahng JW, Overton JM, Houpt TA. Hypothalamic NPY, AGRP, and POMC mRNA responses to leptin and refeeding in mice. Am. J. Physiol. Regul. Integr. Comp. Physiol.283(5), R1020–R1026 (2002).
  • Hagan MM, Rushing PA, Pritchard LM et al. Long-term orexigenic effects of AgRP-(83---132) involve mechanisms other than melanocortin receptor blockade. Am. J. Physiol.279(1), R47–R52 (2000).
  • Rossi M, Kim MS, Morgan DGA et al. A C-terminal fragment of Agouti-related protein increases feeding and antagonizes the effect of α-melanocyte stimulating hormone in vivo.Endocrinology139(10), 4428–4431 (1998).
  • Ollmann MM, Wilson BD, Yang YK et al. Antagonism of central melanocortin receptors in vitro and in vivo by agouti-related protein. Science278(5335), 135–138 (1997).
  • Hahn TM, Breininger JF, Baskin DG, Schwartz MW. Coexpression of Agrp and NPY in fasting-activated hypothalamic neurons. Nat. Neurosci.1(4), 271–272 (1998).
  • Larhammar D. Structural diversity of receptors for neuropeptide Y, peptide YY and pancreatic polypeptide. Regul. Pept.65(3), 165–174 (1996).
  • Inui A. Neuropeptide Y feeding receptors: Are multiple subtypes involved? Trends Pharmacol. Sci.20(2), 43–46 (1999).
  • King PJ, Widdowson PS, Doods HN, Williams G. Regulation of neuropeptide Y release by neuropeptide Y receptor ligands and calcium channel antagonists in hypothalamic slices. J. Neurochem.73(2), 641–646 (1999).
  • Fekete C, Légrádi G, Mihály E et al. α-melanocyte-stimulating hormone is contained in nerve terminals innervating thyrotropin-releasing hormone-synthesizing neurons in the hypothalamic paraventricular nucleus and prevents fasting-induced suppression of prothyrotropin-releasing hormone gene expression. J. Neurosci.20(4), 1550–1558 (2000).
  • Fekete C, Sarkar S, Rand WM et al. Agouti-related protein (AGRP) has a central inhibitory action on the hypothalamic–pituitary–thyroid (HPT) axis; comparisons between the effect of AGRP and neuropeptide Y on energy homeostasis and the HPT axis. Endocrinology143(10), 3846–3853 (2002).
  • Sarkar S, Lechan RM. Central administration of neuropeptide Y reduces α-melanocyte-stimulating hormone-induced cyclic adenosine 5´-monophosphate response element binding protein (CREB). Endocrinology144(1), 281–291 (2003).
  • Qu D, Ludwig DS, Gammeltoft S et al. A role for melanin-concentrating hormone in the central regulation of feeding behaviour. Nature380(6571), 243–247 (1996).
  • Pelleymounter MA, Cullen MJ, Wellman CL. Characteristics of BDNF-induced weight loss. Exp. Neurol.131(2), 229–238 (1995).
  • Yeo GSH, Connie Hung C-C, Rochford J et al. A de novo mutation affecting human TrkB associated with severe obesity and developmental delay. Nat. Neurosci.7(11), 1187–1189 (2004).
  • Xu B, Goulding EH, Zang K et al. Brain-derived neurotrophic factor regulates energy balance downstream of melanocortin-4 receptor. Nat. Neurosci.6(7), 736–742 (2003).
  • Ricardo JA, Tongju Koh E. Anatomical evidence of direct projections from the nucleus of the solitary tract to the hypothalamus, amygdala, and other forebrain structures in the rat. Brain Res.153(1), 1–26 (1978).
  • Ter Horst GJ, De Boer P, Luiten PGM, Van Willigen JD. Ascending projections from the solitary tract nucleus to the hypothalamus. A phaseolus vulgaris lectin tracing study in the rat. Neuroscience31(3), 785–797 (1989).
  • Szczypka MS, Kwok K, Brot MD et al. Dopamine production in the caudate putamen restores feeding in dopamine-deficient mice. Neuron30(3), 819–828 (2001).
  • Hayward MD, Pintar JE, Low MJ. Selective reward deficit in mice lacking β-endorphin and enkephalin. J. Neurosci.22(18), 8251–8258 (2002).
  • Di Marzo V, Matias I. Endocannabinoid control of food intake and energy balance. Nat. Neurosci.8(5), 585–589 (2005).
  • Mashiko S, Moriya R, Ishihara A et al. Synergistic interaction between neuropeptide Y1 and Y5 receptor pathways in regulation of energy homeostasis. Eur. J. Pharmacol.615(1–3), 113–117 (2009).
  • Kanatani A, Mashiko S, Murai N et al. Role of the Y1 receptor in the regulation of neuropeptide Y-mediated feeding: comparison of wild-type, Y1 receptor-deficient, and Y5 receptor-deficient mice. Endocrinology141(3), 1011–1016 (2000).
  • Erondu N, Gantz I, Musser B et al. Neuropeptide Y5 receptor antagonism does not induce clinically meaningful weight loss in overweight and obese adults. Cell Metab.4(4), 275–282 (2006).
  • Sargent BJ, Moore NA. New central targets for the treatment of obesity. Br. J. Clin. Pharmacol.68(6), 852–860 (2009).
  • Borowsky B, Durkin MM, Ogozalek K et al. Antidepressant, anxiolytic and anorectic effects of a melanin-concentrating hormone-1 receptor antagonist. Nat. Med.8(8), 825–830 (2002).
  • Adan RA, Tiesjema B, Hillebrand JJ, Fleur SE, Kas MJ, Krom M. The MC4 receptor and control of appetite. Br. J. Pharmacol.149(7), 815–827 (2006).
  • Mitchell J, Maguire J, Davenport A. Emerging pharmacology and physiology of neuromedin U and the structurally related peptide neuromedin S. Br. J. Pharmacol.158(1), 87–103 (2009).
  • Thompson EL, Murphy KG, Todd JF et al. Chronic administration of NMU into the paraventricular nucleus stimulates the HPA axis but does not influence food intake or bodyweight. Biochem. Biophys. Res. Commun.323(1), 65–71 (2004).
  • Novak CM, Zhang M, Levine JA. Sensitivity of the hypothalamic paraventricular nucleus to the locomotor-activating effects of neuromedin U in obesity. Brain Res.1169(1), 57–68 (2007).
  • Moran TH. Cholecystokinin and satiety: current perspectives. Nutrition16(10), 858–865 (2000).
  • Crawley JN. Biological actions of cholecystokinin. Peptides15(4), 731–755 (1994).
  • Moran TH, Baldessarini AR, Salorio CF, Lowery T, Schwartz GJ. Vagal afferent and efferent contributions to the inhibition of food intake by cholecystokinin. Am. J. Physiol. Regul. Integr. Comp. Physiol.272(4), 41–44 (1997).
  • Moran TH, Shnayder L, Hostetler AM, McHugh PR. Pylorectomy reduces the satiety action of cholecystokinin. Am. J. Physiol. Regul. Integr. Comp. Physiol.255(6) (1988).
  • Moran TH, Bi S. Hyperphagia and obesity in OLETF rats lacking CCK-1 receptors. Philos. Trans. R. Soc. Lond. B. Biol. Sci.361(1471), 1211–1218 (2006).
  • 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. Regul. Integr. Comp. Physiol.280(4), 49–44 (2001).
  • Asin KE, Bednarz L. Differential effects of CCK-JMV-180 on food intake in rats and mice. Pharmacol. Biochem. Behav.42(2), 291–295 (1992).
  • Crawley JN, Beinfeld MC. Rapid development of tolerance to the behavioural actions of cholecystokinin. Nature302(5910), 703–706 (1983).
  • Lukaszewski L, Praissman M. Effect of continuous infusions of CCK-8 on food intake and body and pancreatic weights in rats. Am. J. Physiol. Regul. Integr. Comp. Physiol.254(1), R17–R22 (1988).
  • West DB, Fey D, Woods SC. Cholecystokinin persistently suppresses meal size but not food intake in free-feeding rats. Am. J. Physiol. Regul. Integr. Comp. Physiol.15(5), R776–R787 (1984).
  • Fong TM. Advances in anti-obesity therapeutics. Expert Opin. Investig. Drugs14(3), 243–250 (2005).
  • Matson CA, Ritter RC. Long-term CCK-leptin synergy suggests a role for CCK in the regulation of bodyweight. Am. J. Physiol. Regul. Integr. Comp. Physiol.276(4), 45–44 (1999).
  • Plusczyk T, Westermann S, Rathgeb D, Feifel G. Acute pancreatitis in rats: effects of sodium taurocholate, CCK-8, and Sec on pancreatic microcirculation. Am. J. Physiol.272(2 Pt 1), G310–G320 (1997).
  • Pandol SJ, Periskic S, Gukovsky I et al. Ethanol diet increases the sensitivity of rats to pancreatitis induced by cholecystokinin octapeptide. Gastroenterology117(3), 706–716 (1999).
  • Drucker DJ. The biology of incretin hormones. Cell Metab.3(3), 153–165 (2006).
  • Brubaker PL. The glucagon-like peptides: pleiotropic regulators of nutrient homeostasis. Ann. NY Acad. Sci.1070, 10–26 (2006).
  • Baggio LL, Drucker DJ. Biology of incretins: GLP-1 and GIP. Gastroenterology132(6), 2131–2157 (2007).
  • Meeran K, O’Shea D, Edwards CMB et al. Repeated intracerebroventricular administration of glucagon-like peptide-1-(7–36) amide or exendin-(9–39) alters bodyweight in the rat. Endocrinology140(1), 244–250 (1999).
  • Turton MD, O’Shea D, Gunn I et al. A role for glucagon-like peptide-1 in the central regulation of feeding. Nature379(6560), 69–72 (1996).
  • Flint A, Raben A, Astrup A, Holst JJ. Glucagon-like peptide 1 promotes satiety and suppresses energy intake in humans. J. Clin. Invest.101(3), 515–520 (1998).
  • Näslund E, King N, Mansten S et al. Prandial subcutaneous injections of glucagon-like peptide-1 cause weight loss in obese human subjects. Br. J. Nutr.91(3), 439–446 (2004).
  • Tang-Christensen M, Vrang N, Larsen PJ. Glucagon-like peptide 1(7–36) amide’s central inhibition of feeding and peripheral inhibition of are abolished by neonatal monosodium glutamate treatment. Diabetes47(4), 530–537 (1998).
  • Abbott CR, Monteiro M, Small CJ 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(1), 127–131 (2005).
  • Furuse M, Matsumoto M, Mori R, Sugahara K, Kano K, Hasegawa S. Influence of fasting and neuropeptide Y on the suppressive food intake induced by intracerebroventricular injection of glucagon-like peptide-1 in the neonatal chick. Brain Res.764(1–2), 289–292 (1997).
  • Mentlein R, Gallwitz B, Schmidt WE. Dipeptidyl-peptidase IV hydrolyses gastric inhibitory polypeptide, glucagon-like peptide-1(7–36)amide, peptide histidine methionine and is responsible for their degradation in human serum. Eur. J. Biochem.214(3), 829–835 (1993).
  • Amori RE, Lau J, Pittas AG. Efficacy and safety of incretin therapy in Type 2 diabetes: systematic review and meta-analysis. JAMA298(2), 194–206 (2007).
  • Astrup A, Rössner S, Van Gaal L et al. Effects of liraglutide in the treatment of obesity: a randomised, double-blind, placebo-controlled study. Lancet374(9701), 1606–1616 (2009).
  • Bailey CJ, Turner RC. Metformin. N. Engl. J. Med.334(9), 574–579 (1996).
  • Avenell A, Brown TJ, McGee MA et al. What interventions should we add to weight reducing diets in adults with obesity? A systematic review of randomized controlled trials of adding drug therapy, exercise, behaviour therapy or combinations of these interventions. J. Hum. Nutr. Diet17(4), 293–316 (2004).
  • Kim D, MacConell L, Zhuang D et al. Effects of once-weekly dosing of a long-acting release formulation of exenatide on glucose control and bodyweight in subjects with Type 2 diabetes. Diabetes Care30(6), 1487–1493 (2007).
  • Beglinger C, Poller B, Arbit E et al. Pharmacokinetics and pharmacodynamic effects of oral GLP-1 and PYY3–36: a proof-of-concept study in healthy subjects. Clin. Pharmacol. Ther.84(4), 468–474 (2008).
  • Dore DD, Seeger JD, Arnold Chan K. Use of a claims-based active drug safety surveillance system to assess the risk of acute pancreatitis with exenatide or sitagliptin compared with metformin or glyburide. Curr. Med. Res. Opin.25(4), 1019–1027 (2009).
  • Gallwitz B. Benefit-risk assessment of exenatide in the therapy of Type 2 diabetes mellitus. Drug Saf.33(2), 87–100 (2010).
  • Dakin CL, Gunn I, Small CJ et al. Oxyntomodulin inhibits food intake in the rat. Endocrinology142(10), 4244–4250 (2001).
  • Dakin CL, Small CJ, Batterham RL et al. Peripheral oxyntomodulin reduces food intake and bodyweight gain in rats. Endocrinology145(6), 2687–2695 (2004).
  • Cohen MA, Ellis SM, Le Roux CW et al. Oxyntomodulin suppresses appetite and reduces food intake in humans. J. Clin. Endocrinol. Metab.88(10), 4696–4701 (2003).
  • Baggio LL, Huang Q, Brown TJ, Drucker DJ. Oxyntomodulin and glucagon-like peptide-1 differentially regulate murine food intake and energy expenditure. Gastroenterology127(2), 546–558 (2004).
  • Wynne K, Park AJ, Small CJ et al. Subcutaneous oxyntomodulin reduces bodyweight in overweight and obese subjects: a double-blind, randomized, controlled trial. Diabetes54(8), 2390–2395 (2005).
  • Wynne K, Park AJ, Small CJ et al. Oxyntomodulin increases energy expenditure in addition to decreasing energy intake in overweight and obese humans: a randomised controlled trial. Int J. Obes.30(12), 1729–1736 (2006).
  • Adrian TE, Ferri GL, Bacarese-Hamilton AJ. Human distribution and release of a putative new gut hormone, peptide YY. Gastroenterology89(5), 1070–1077 (1985).
  • Liu CD, Aloia T, Adrian TE et al. Peptide YY: a potential proabsorptive hormone for the treatment of malabsorptive disorders. Am. Surg.62(3), 232–236 (1996).
  • Adrian TE, Savage AP, Sagor GR. Effect of peptide YY on gastric, pancreatic, and biliary function in humans. Gastroenterology89(3), 494–499 (1985).
  • Adams SH, Won WB, Schonhoff SE, Leiter AB, Paterniti JR Jr. Effects of peptide YY(3–36) on short-term food intake in mice are not affected by prevailing plasma ghrelin levels. Endocrinology145(11), 4967–4975 (2004).
  • Chelikani PK, Haver AC, Heidelberger RD. Intravenous infusion of peptide YY(3–36) potently inhibits food intake in rats. Endocrinology146(2), 879–888 (2005).
  • Batterham RL, Cowley MA, Small CJ et al. Gut hormone PYY3–36 physiologically inhibits food intake. Nature418(6898), 650–654 (2002).
  • Batterham RL, Heffron H, Kapoor S et al. Critical role for peptide YY in protein-mediated satiation and body-weight regulation. Cell Metab.4(3), 223–233 (2006).
  • Le Roux CW, Batterham RL, Aylwin SJB et al. Attenuated peptide YY release in obese subjects is associated with reduced satiety. Endocrinology147(1), 3–8 (2006).
  • Wren AM, Bloom SR. Gut hormones and appetite control. Gastroenterology132(6), 2116–2130 (2007).
  • Batterham RL, Cohen MA, Ellis SM et al. Inhibition of food intake in obese subjects by peptide YY3-36. N. Engl. J. Med.349(10), 941–948 (2003).
  • Degen L, Oesch S, Casanova M et al. Effect of peptide YY3-36 on food intake in humans. Gastroenterology129(5), 1430–1436 (2005).
  • Gantz I, Erondu N, Mallick M et al. Efficacy and safety of intranasal peptide YY3-36 for weight reduction in obese adults. J. Clin. Endocrinol. Metab.92(5), 1754–1757 (2007).
  • Kojima M, Hosoda H, Date Y, Nakazato M, Matsuo H, Kangawa K. Ghrelin is a growth-hormone-releasing acylated peptide from stomach. Nature402(6762), 656–660 (1999).
  • Sun Y, Ahmed S, Smith RG. Deletion of ghrelin impairs neither growth nor appetite. Cell. Mol. Biol.23(22), 7973–7981 (2003).
  • Tschop M, Smiley DL, Heiman ML. Ghrelin induces adiposity in rodents. Nature407(6806), 908–913 (2000).
  • Wren AM, Small CJ, Abbott CR et al. Ghrelin causes hyperphagia and obesity in rats. Diabetes50(7–12), 2540–2547 (2001).
  • Tschöp M, Weyer C, Tataranni PA, Devanarayan V, Ravussin E, Heiman ML. Circulating ghrelin levels are decreased in human obesity. Diabetes50(4), 707–709 (2001).
  • Otto B, Cuntz U, Fruehauf E et al. Weight gain decreases elevated plasma ghrelin concentrations of patients with anorexia nervosa. Eur. J. Endocrinol.145(5), 669–673 (2001).
  • Tolle V, Kadem M, Bluet-Pajot MT et al. Balance in ghrelin and leptin plasma levels in anorexia nervosa patients and constitutionally thin women. J. Clin. Endocrinol. Metab.88(1), 109–116 (2003).
  • Guan XM, Yu H, Palyha OC et al. Distribution of mRNA encoding the growth hormone secretagogue receptor in brain and peripheral tissues. Mol. Brain Res.48(1), 23–29 (1997).
  • Gnanapavan S, Kola B, Bustin SA et al. The tissue distribution of the mRNA of ghrelin and subtypes of its receptor, GHS-R, in humans. J. Clin. Endocrinol. Metab.87(6), 2988–2991 (2002).
  • Date Y, Murakami N, Toshinai K et al. The role of the gastric afferent vagal nerve in ghrelin-induced feeding and growth hormone secretion in rats. Gastroenterology123(4), 1120–1128 (2002).
  • Naleid AM, Grace MK, Cummings DE, Levine AS. Ghrelin induces feeding in the mesolimbic reward pathway between the ventral tegmental area and the nucleus accumbens. Peptides26(11), 2274–2279 (2005).
  • Carlini VP, Varas MM, Cragnolini AB, Schiöth HB, Scimonelli TN, De Barioglio SR. Differential role of the hippocampus, amygdala, and dorsal raphe nucleus in regulating feeding, memory, and anxiety-like behavioral responses to ghrelin. Biochem. Biophys. Res. Commun.313(3), 635–641 (2004).
  • Zorrilla EP, Iwasaki S, Moss JA et al. Vaccination against weight gain. Proc. Natl Acad. Sci. USA103(35), 13226–13231 (2006).
  • Moran TH, Dailey MJ. Gut peptides: targets for antiobesity drug development? Endocrinology150(6), 2526–2530 (2009).
  • Yang J, Zhao T-J, Goldstein JL, Brown MS. Inhibition of ghrelin -acyltransferase (GOAT) by octanoylated pentapeptides. Proc. Natl Acad. Sci. USA105(31), 10750–10755 (2008).
  • Hort Y, Baker E, Sutherland GR, Shine J, Herzog H. Gene duplication of the human peptide YY gene (PYY) generated the pancreatic polypeptide gene (PPY) on chromosome 17q21.1. Genomics26(1), 77–83 (1995).
  • Adrian TE, Bloom SR, Bryant MG. Distribution and release of human pancreatic polypeptide. Gut17(12), 940–944 (1976).
  • Chaudhri O, Small C, Bloom S. Gastrointestinal hormones regulating appetite. Philos. Trans. R. Soc. Lond. B. Biol. Sci.361(1471), 1187–1209 (2006).
  • Malaisse-Lagae F, Carpentier JL, Patel YC. Pancreatic polypeptide: a possible role in the regulation of food intake in the mouse. Hypothesis. Experientia33(7), 915–917 (1977).
  • Asakawa A, Inui A, Yuzuriha H et al. Characterization of the effects of pancreatic polypeptide in the regulation of energy balance. Gastroenterology124(5), 1325–1336 (2003).
  • Ueno N, Inui A, Iwamoto M et al. Decreased food intake and bodyweight in pancreatic polypeptide-overexpressing mice. Gastroenterology117(6), 1427–1432 (1999).
  • Reinehr T, Enriori PJ, Harz K, Cowley MA, Roth CL. Pancreatic polypeptide in obese children before and after weight loss. Int. J. Obes.30(10), 1476–1481 (2006).
  • Fujimoto S, Inui A, Kiyota N et al. Increased cholecystokinin and pancreatic polypeptide responses to a fat-rich meal in patients with restrictive but not bulimic anorexia nervosa. Biol. Psychiatry41(10), 1068–1070 (1997).
  • Reinehr T, Enriori PJ, Harz K, Cowley MA, Roth CL. Pancreatic polypeptide in obese children before and after weight loss. Int. J. Obes.30(10), 1476–1481 (2006).
  • Clark JT, Kalra PS, Crowley WR, Kalra SP. Neuropeptide Y and human pancreatic polypeptide stimulate feeding behavior in rats. Endocrinology115(1), 427–429 (1984).
  • Larsen PJ, Kristensen P. The neuropeptide Y (Y4) receptor is highly expressed in neurones of the rat dorsal vagal complex. Mol. Brain Res.48(1), 1–6 (1997).
  • Whitcomb DC, Taylor IL, Vigna SR. Characterization of saturable binding sites for circulating pancreatic polypeptide in rat brain. Am. J. Physiol. Gastrointest. Liver Physiol.259(4), 22–24 (1990).
  • Batterham RL, Le Roux CW, Cohen MA et al. Pancreatic polypeptide reduces appetite and food intake in humans. J. Clin. Endocrinol. Metab.88(8), 3989–3992 (2003).
  • Adrian TE, Greenberg GR, Besterman HS, Bloom SR. Pharmacokinetics of pancreatic polypeptide in man. Gut19(10), 907–909 (1978).
  • Pittner RA, Albrandt K, Beaumont K et al. Molecular physiology of amylin. Cell. Physiol. Biochem.55(Suppl.), 19–28 (1994).
  • Koda JE, Fineman M, Rink TJ, Dailey GE, Muchmore DB, Linarelli LG. Amylin concentrations and glucose control. Lancet339(8802), 1179–1180 (1992).
  • Koda JE, Fineman MS, Kolterman OG, Caro JF. 24 hour plasma amylin profiles are elevated in IGT subjects vs. normal controls. Diabetes44(Suppl. 1) (1995).
  • Rushing PA, Hagan MM, Seeley RJ, Lutz TA, Woods SC. Amylin: a novel action in the brain to reduce bodyweight. Endocrinology141(2), 850–853 (2000).
  • Rushing PA, Hagan MM, Seeley RJ et al. Inhibition of central amylin signaling increases food intake and body adiposity in rats. Endocrinology142(11), 5035–5038 (2001).
  • Gebre-Medhin S, Mulder H, Pekny M et al. IAPP (amylin) null mutant mice; plasma levels of insulin and glucose, bodyweight and pain responses. Diabetologia40, 29A (1997).
  • Devine E, Young AA. Weight gain in male and female mice with amylin gene knockout. Diabetes47(Suppl. 1), A317 (1998).
  • Cooper GJ. Amylin compared with calcitonin gene-related peptide: structure, biology, and relevance to metabolic disease. Endocr. Rev.15(2), 163–201 (1994).
  • Young AA, Wang MW, Gedulin B, Rink TJ, Pittner R, Beaumont K. Diabetogenic effects of salmon calcitonin are attributable to amylin-like activity. Metab. Clin. Exp.44(12), 1581–1589 (1995).
  • McLatchie LM, Fraser NJ, Main MJ et al. RAMPS regulate the transport and ligand specificity of the calcitonin-receptor-like receptor. Nature393(6683), 333–339 (1998).
  • Muff R, Bühlmann N, Fischer JA, Born W. An amylin receptor is revealed following co-transfection of a calcitonin receptor with receptor activity modifying proteins-1 or -3. Endocrinology140(6), 2924–2927 (1999).
  • Poyner D, Marshall I, Brain SD et al.The CGRP Family: Calcitonin Gene- Related Peptide (CGRP), Amylin, and Adrenomedullin. Poyner D et al. (Eds). Landes Bioscience, TX, USA 1–258 (2000).
  • Jodka C, Green D, Young A, Gedulin B. Amylin modulation of gastric emptying in rats depends upon an intact vagus nerve. Diabetes45(Suppl. 1), A235 (1996).
  • Edwards GL, Gedulin BR, Jodka C, Dilts RP, Miller CC, Young A. Area postrema (AP)-lesions block the regulation of gastric emptying by amylin. Neurogastroenterol. Motil.10(4), 26 (1998).
  • Lutz TA, Mollet A, Rushing PA, Riediger T, Scharrer E. The anorectic effect of a chronic peripheral infusion of amylin is abolished in area postrema/nucleus of the solitary tract (AP/NTS) lesioned rats. Int. J. Obes.25(7), 1005–1011 (2001).
  • Edelman SV, Weyer C. Unresolved challenges with insulin therapy in Type 1 and Type 2 diabetes: potential benefit of replacing amylin, a second β-cell hormone. Diabetes Technol. Ther.4(2), 175–189 (2002).
  • Young AA, Vine W, Gedulin BR et al. Preclinical pharmacology of pramlintide in the rat: comparisons with human and rat amylin. Drug Dev. Res.37(4), 231–248 (1996).
  • Ratner RE, Want LL, Fineman MS et al. Adjunctive therapy with the amylin analog pramlintide leads to a combined improvement in glycemic and weight control in insulin-treated subjects with Type 2 diabetes. Diabetes Technol. Ther.4(1), 51–61 (2002).
  • Hollander PA, Levy P, Fineman MS et al. Pramlintide as an adjunct to insulin therapy improves long-term glycemic and weight control in patients with Type 2 diabetes. Diabetes Care26(3), 784–790 (2003).
  • Whitehouse F, Kruger DF, Fineman M 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 Care25(4), 724–730 (2002).
  • Maggs D, Shen L, Strobel S, Brown D, Kolterman O, Weyer C. Effect of pramlintide on A1C and bodyweight in insulin-treated African Americans and Hispanics with Type 2 diabetes: a pooled post hoc analysis. Metabolism52(12), 1638–1642 (2003).
  • Ingalls AM, Dickie MM, Snell GD. Obese, a new mutation in the house mouse. Obes. Res.4(1), 101 (1996).
  • Zhang Y, Proenca R, Maffei M, Barone M, Leopold L, Friedman JM. Positional cloning of the mouse obese gene and its human homologue. Nature372(6505), 425–432 (1994).
  • Halaas JL, Gajiwala KS, Maffei M et al. Weight-reducing effects of the plasma protein encoded by the obese gene. Science269(5223), 543–546 (1995).
  • Pelleymounter MA, Cullen MJ, Baker MB et al. Effects of the obese gene product on bodyweight regulation in ob /ob mice. Science269(5223), 540–543 (1995).
  • Montague CT, Farooqi IS, Whitehead JP et al. Congenital leptin deficiency is associated with severe early-onset obesity in humans. Nature387(6636), 903–908 (1997).
  • Farooqi IS, O’Rahilly S. Monogenic obesity in humans. 56, 443–458 (2005).
  • Considine RV, Sinha MK, Heiman ML et al. Serum immunoreactive-leptin concentrations in normal-weight and obese humans. N. Engl. J. Med.334(5), 292–295 (1996).
  • Ahlma RS, Prabakaran D, Mantzoros C et al. Role of leptin in the neuroendocrine response to fasting. Nature382(6588), 250–252 (1996).
  • Tartaglia LA, Dembski M, Weng X et al. Identification and expression cloning of a leptin receptor, OB-R. Cell83(7), 1263–1271 (1995).
  • Münzberg H, Myers MG Jr. Molecular and anatomical determinants of central leptin resistance. Nat. Neurosci.8(5), 566–570 (2005).
  • Myers MG Jr. Leptin receptor signaling and the regulation of mammalian physiology. Recent Prog. Horm. Res.59(1), 287–304 (2004).
  • Morris DL, Rui L. Recent advances in understanding leptin signaling and leptin resistance. Am. J. Physiol. Endocrinol. Metab.297(6), E1247–E1259 (2009).
  • Cheung CC, Clifton DK, Steiner RA. Proopiomelanocortin neurons are direct targets for leptin in the hypothalamus. Endocrinology138(10), 4489–4492 (1997).
  • Baskin DG, Breininger JF, Schwartz MW. Leptin receptor mRNA identifies a subpopulation of neuropeptide y neurons activated by fasting in rat hypothalamus. Diabetes48(4), 828–833 (1999).
  • Tang-Christensen M, Holst JJ, Hartmann B, Vrang N. The arcuate nucleus is pivotal in mediating the anorectic effects of centrally administered leptin. NeuroReport10(6), 1183–1187 (1999).
  • Schwartz MW, Baskin DG, Bukowski TR et al. Specificity of leptin action on elevated blood glucose levels and hypothalamic neuropeptide Y gene expression in ob /ob mice. Diabetes45(4), 531–535 (1996).
  • Stephens TW, Basinski M, Bristow PK et al. The role of neuropeptide Y in the antiobesity action of the obese gene product. Nature377(6549), 530–532 (1995).
  • Schwartz MW, Seeley RJ, Woods SC et al. Leptin increases hypothalamic pro-opiomelanocortin mRNA expression in the rostral arcuate nucleus. Diabetes46(12), 2119–2123 (1997).
  • Ozcan L, Ergin AS, Lu A et al. Endoplasmic reticulum stress plays a central role in development of leptin resistance. Cell Metab.9(1), 35–51 (2009).
  • Hukshorn CJ, Saris WHM, Westerterp-Plantenga MS, Farid AR, Smith FJ, Campfield LA. Weekly subcutaneous pegylated recombinant native human leptin (PEG-OB) administration in obese men. J. Clin. Endocrinol. Metab.85(11), 4003–4009 (2000).
  • Roth JD, Roland BL, Cole RL et al. Leptin responsiveness restored by amylin agonism in diet-induced obesity: evidence from nonclinical and clinical studies. Proc. Natl Acad. Sci. USA105(20), 7257–7262 (2008).
  • Gadde KM, Allison DB. Combination therapy for obesity and metabolic disease. Curr. Opin. Endocrinol. Diabetes Obes.16(5), 353–358 (2009).
  • Fernández-Real JM, Sanchis D, Ricart W et al. Plasma oestrone-fatty acid ester levels are correlated with body fat mass in humans. Clin. Endocrinol.50(2), 253–260 (1999).
  • Sanchis D, Balada F, Del Mar Grasa M et al. Oleoyl-estrone induces the loss of body fat in rats. Int. J. Obes.20(6), 588–594 (1996).
  • Sanchis D, Balada F, Picó C et al. Rats receiving the slimming agent oleoyl-estrone in liposomes (Merlin-2) decrease food intake but maintain thermogenesis. Arch. Physiol. Biochem.105(7), 663–672 (1997).
  • Adán C, Cabot C, Vilà R et al. Oleoyl-estrone treatment affects the ponderostat setting differently in lean and obese Zucker rats. Int. J. Obes.23(4), 366–373 (1999).
  • Remesar X, Guijarro P, Torregrosa C et al. Oral oleoyl-estrone induces the rapid loss of body fat in Zucker lean rats fed a hyperlipidic diet. Int. J. Obes.24(11), 1405–1412 (2000).
  • Alemany M, Fernández-López JA, Petrobelli A, Granada M, Foz M, Remesar X. [Weight loss in a patient with morbid obesity under treatment with oleoyl-estrone]. Med. Clin. (Barc.)121(13), 496–499 (2003).
  • Sonnenberg GE, Matfin G, Reinhardt RR. Drug treatments for obesity: where are we heading and how do we get there? Br. J. Diabetes Vasc. Dis.7(3), 111–118 (2007).
  • Bray GA, Greenway FL. Current and potential drugs for treatment of obesity. Endocr. Rev.20(6), 805–875 (1999).

Websites

Reprints and Corporate Permissions

Please note: Selecting permissions does not provide access to the full text of the article, please see our help page How do I view content?

To request a reprint or corporate permissions for this article, please click on the relevant link below:

Academic Permissions

Please note: Selecting permissions does not provide access to the full text of the article, please see our help page How do I view content?

Obtain permissions instantly via Rightslink by clicking on the button below:

If you are unable to obtain permissions via Rightslink, please complete and submit this Permissions form. For more information, please visit our Permissions help page.