Publication Cover
Nutritional Neuroscience
An International Journal on Nutrition, Diet and Nervous System
Volume 27, 2024 - Issue 1
434
Views
5
CrossRef citations to date
0
Altmetric
Review

Leptin and energy balance: exploring Leptin’s role in the regulation of energy intake and energy expenditure

, , & ORCID Icon

References

  • WHO. Obesity and Overweight. Geneva: World Health Organization; 2021 [cited 2022 June 12]. Available from: https://www.who.int/news-room/fact-sheets/detail/obesity-and-overweight.
  • Djalalinia S, Qorbani M, Peykari N, Kelishadi R. Health impacts of Obesity. Pak J Med Sci. 2015;31(1):239–42.
  • Hill JO, Wyatt HR, Peters JC. Energy balance and obesity. Circulation. 2012;126(1):126–32. doi:10.1161/circulationaha.111.087213.
  • Ahima RS, Antwi DA. Brain regulation of appetite and satiety. Endocrinol Metab Clin North Am. 2008;37(4):811–23. doi:10.1016/j.ecl.2008.08.005.
  • Friedman J. The long road to leptin. J Clin Invest. 2016;126(12):4727–34.
  • Huang L, Wang Z, Li C. Modulation of circulating leptin levels by its soluble receptor. J Biol Chem. 2001;276(9):6343–9.
  • Klok MD, Jakobsdottir S, Drent ML. The role of leptin and ghrelin in the regulation of food intake and body weight in humans: a review. Obes Rev. 2007;8(1):21–34.
  • Pandit, R., Beerens, S., and Adan, R.A.H. 2017. Role of leptin in energy expenditure: the hypothalamic perspective. Am J Physiol Regul Integr Comp Physiol 312(6): R938–R947.
  • Druce M, Bloom SR. The regulation of appetite. Arch Dis Child. 2005;91(2):183–7.
  • Woods SC, D'Alessio DA. Central control of body weight and appetite. J Clin Endocrinol Metab. 2008;93(11 Suppl 1):S37–50.
  • de Lartigue G, Barbier de la Serre C, Espero E, Lee J, Raybould HE. Leptin resistance in vagal afferent neurons inhibits cholecystokinin signaling and satiation in diet induced obese rats. PLoS One. 2012;7(3):e32967–e32967.
  • Heldsinger A, Grabauskas G, Song I, Owyang C. Synergistic interaction between leptin and cholecystokinin in the Rat nodose ganglia Is mediated by PI3K and STAT3 signaling pathways. J Biol Chem. 2011;286(13):11707–15.
  • Liu J, Yang X, Yu S, Zheng R. The leptin resistance. Adv Exp Med Biol. 2018;1090:145–63.
  • Abdalla MM. Central and peripheral control of food intake. Endocr Regul. 2017;51(1):52–70. doi:10.1515/enr-2017-0006.
  • Browning KN, Verheijden S, Boeckxstaens GE. The vagus nerve in appetite regulation, mood, and intestinal inflammation. Gastroenterology. 2017;152(4):730–44. doi:10.1053/j.gastro.2016.10.046.
  • Austin J, Marks D. Hormonal regulators of appetite. Int J Pediatr Endocrinol. 2009: 141753. doi:10.1155/2009/141753.
  • Kelesidis T, Kelesidis I, Chou S, Mantzoros CS. Narrative review: the role of leptin in human physiology: emerging clinical applications. Ann Intern Med. 2010;152(2):93–100.
  • Blevins JE, Baskin DG. Forum of nutrition. Forum Nutr. 2010;63:133–40. doi:10.1159/000264401.
  • Cammisotto PG, Levy E, Bukowiecki LJ, Bendayan M. Cross-talk between adipose and gastric leptins for the control of food intake and energy metabolism. Prog Histochem Cytochem. 2010;45(3):143–200. doi:10.1016/j.proghi.2010.06.001.
  • Nunziata A, Funcke JB, Borck G, von Schnurbein J, Brandt S, Lennerz B, et al. Functional and phenotypic characteristics of human leptin receptor mutations. J Endocr Soc. 2018;3(1):27–41.
  • Gorska E, Popko K, Stelmaszczyk-Emmel A, Ciepiela O, Kucharska A, Wasik M. Leptin receptors. Eur J Med Res. 2010;15(Suppl 2):50–4.
  • Tartaglia LA, Dembski M, Weng X, Deng N, Culpepper J, Devos R, et al. Identification and expression cloning of a leptin receptor, OB-R. Cell. 1995;83(7):1263–71.
  • Peng J, Yin L, Wang X. Central and peripheral leptin resistance in obesity and improvements of exercise. Horm Behav. 2021;133:105006.
  • Heiman ML, Ahima RS, Craft LS, Schoner B, Stephens TW, Flier JS. Leptin inhibition of the hypothalamic-pituitary-adrenal axis in response to stress1. Endocrinology. 1997;138(9):3859–63.
  • Robertson SA, Leinninger GM, Myers MG, Jr. Molecular and neural mediators of leptin action. Physiol Behav. 2008;94(5):637–42.
  • Bates S, Myers M. The role of leptin receptor signaling in feeding and neuroendocrine function. Trends Endocrinol Metab. 2003;14:447–52. doi:10.1016/j.tem.2003.10.003.
  • Amitani M, Asakawa A, Amitani H, Inui A. The role of leptin in the control of insulin-glucose axis. Front Neurosci. 2013;7:51–. doi:10.3389/fnins.2013.00051.
  • Wang Y, Kuropatwinski KK, White DW, Hawley TS, Hawley RG, Tartaglia LA, et al. Leptin receptor action in hepatic cells. J Biol Chem. 1997;272(26):16216–23.
  • Barazzoni R, Zanetti M, Stebel M, Biolo G, Cattin L, Guarnieri G. Hyperleptinemia prevents increased plasma ghrelin concentration during short-term moderate caloric restriction in rats. Gastroenterology. 2003;124(5):1188–92. doi:10.1016/S0016-5085(03)00281-6.
  • Beretta E, Dube MG, Kalra PS, Kalra SP. Long-Term suppression of weight gain, adiposity, and serum insulin by central leptin gene therapy in prepubertal rats: effects on serum ghrelin and appetite-regulating genes. Pediatric Res. 2002;52(2):189–98. doi:10.1203/00006450-200208000-00010.
  • Dube MG, Beretta E, Dhillon H, Ueno N, Kalra PS, Kalra SP. Central leptin gene therapy blocks high-Fat diet-induced weight gain, hyperleptinemia, and hyperinsulinemia. Diabetes. 2002;51(6):1729–36.
  • Ueno N, Dube MG, Inui A, Kalra PS, Kalra SP. Leptin modulates orexigenic effects of ghrelin and attenuates adiponectin and insulin levels and selectively the dark-phase feeding as revealed by central leptin gene therapy. Endocrinology. 2004;145(9):4176–84.
  • Kohno D, Nakata M, Maekawa F, Fujiwara K, Maejima Y, Kuramochi M, et al. Leptin suppresses ghrelin-induced activation of neuropeptide Y neurons in the arcuate nucleus via phosphatidylinositol 3-kinase- and phosphodiesterase 3-mediated pathway. Endocrinology. 2007;148(5):2251–63.
  • Nakazato M, Murakami N, Date Y, Kojima M, Matsuo H, Kangawa K, et al. A role for ghrelin in the central regulation of feeding. Nature. 2001;409(6817):194–8.
  • Williams DL, Baskin DG, Schwartz MW. Leptin regulation of the anorexic response to glucagon-like peptide-1 receptor stimulation. Diabetes. 2006;55(12):3387–93.
  • Clemmensen C, Chabenne J, Finan B, Sullivan L, Fischer K, Küchler D, et al. GLP-1/glucagon coagonism restores leptin responsiveness in obese mice chronically maintained on an obesogenic diet. Diabetes. 2014;63(4):1422–7.
  • Iepsen EW, Lundgren J, Dirksen C, Jensen JE, Pedersen O, Hansen T, et al. Treatment with a GLP-1 receptor agonist diminishes the decrease in free plasma leptin during maintenance of weight loss. Int J Obes (Lond). 2015;39(5):834–41.
  • Ronveaux CC, Tomé D, Raybould HE. Glucagon-Like peptide 1 interacts with ghrelin and leptin to regulate glucose metabolism and food intake through vagal afferent neuron signaling. J Nutr. 2015;145(4):672–80.
  • Kratzsch J, Lammert A, Bottner A, Seidel B, Mueller G, Thiery J, et al. Circulating soluble leptin receptor and free leptin index during childhood, puberty, and adolescence. J Clin Endocrinol Metab. 2002;87(10):4587–94.
  • Scott MM, Williams KW, Rossi J, Lee CE, Elmquist JK. Leptin receptor expression in hindbrain Glp-1 neurons regulates food intake and energy balance in mice. J Clin Invest. 2011;121(6):2413–21. doi:10.1172/jci43703.
  • Zhao S, Kanoski SE, Yan J, Grill HJ, Hayes MR. Hindbrain leptin and glucagon-like-peptide-1 receptor signaling interact to suppress food intake in an additive manner. Int J Obes (Lond). 2012;36(12):1522–8.
  • Barrachina MD, Martínez V, Wang L, Wei JY, Taché Y. Synergistic interaction between leptin and cholecystokinin to reduce short-term food intake in lean mice. Proc Natl Acad Sci USA. 1997;94(19):10455–60. doi:10.1073/pnas.94.19.10455.
  • Akieda-Asai S, Poleni PE, Date Y. Coinjection of CCK and leptin reduces food intake via increased CART/TRH and reduced AMPK phosphorylation in the hypothalamus. Am J Physiol Endocrinol Metab. 2014;306(11):E1284–1291. doi:10.1152/ajpendo.00664.2013.
  • Huang KP, Ronveaux CC, de Lartigue G, Geary N, Asarian L, Raybould HE. Deletion of leptin receptors in vagal afferent neurons disrupts estrogen signaling, body weight, food intake and hormonal controls of feeding in female mice. Am J Physiol Endocrinol Metab. 2019;316(4):E568–e577.
  • Cork S. The role of the vagus nerve in appetite control: Implications for the pathogenesis of obesity. J Neuroendocrinol. 2018;30:e12643.
  • Valassi E, Scacchi M, Cavagnini F. Neuroendocrine control of food intake. Nutr Metab Cardiovasc Dis. 2008;18(2):158–68.
  • Peters JH, Karpiel AB, Ritter RC, Simasko SM. Cooperative activation of cultured vagal afferent neurons by leptin and cholecystokinin. Endocrinology. 2004;145(8):3652–7.
  • Burdyga G, de Lartigue G, Raybould HE, Morris R, Dimaline R, Varro A, et al. Cholecystokinin regulates expression of Y2 receptors in vagal afferent neurons serving the stomach. J Neurosci. 2008;28(45):11583–92. doi:10.1523/JNEUROSCI.2493-08.2008.
  • Cordeira J, Rios M. Weighing in the role of BDNF in the central control of eating behavior. Mol Neurobiol. 2011;44(3):441–8.
  • Unniappan S, Kieffer TJ. Leptin extends the anorectic effects of chronic PYY(3-36) administration in ad libitum-fed rats. Am J Physiol Regul Integr Comp Physiol. 2008;295(1):R51–58.
  • Rios M. BDNF and the central control of feeding: accidental bystander or essential player? Trends Neurosci. 2013;36(2):83–90.
  • Bariohay B, Lebrun B, Moyse E, Jean A. Brain-Derived neurotrophic factor plays a role as an anorexigenic factor in the dorsal vagal complex. Endocrinology. 2005;146(12):5612–20. doi:10.1210/en.2005-0419.
  • Kernie SG, Liebl DJ, Parada LF. BDNF regulates eating behavior and locomotor activity in mice. Embo J. 2000;19(6):1290–300.
  • Unger, T.J., Calderon, G.A., Bradley, L.C., Sena-Esteves, M., and Rios, M. 2007. Selective deletion of >BDNF< in the ventromedial and dorsomedial hypothalamus of adult mice results in hyperphagic behavior and obesity. J Neurosci 27(52): 14265.
  • Stranahan AM, Lee K, Martin B, Maudsley S, Golden E, Cutler RG, et al. Voluntary exercise and caloric restriction enhance hippocampal dendritic spine density and BDNF levels in diabetic mice. Hippocampus. 2009;19(10):951–61.
  • Liao GY, An JJ, Gharami K, Waterhouse EG, Vanevski F, Jones KR, et al. Dendritically targeted Bdnf mRNA is essential for energy balance and response to leptin. Nat Med. 2012;18(4):564–71.
  • Shin SK, Song SE, Oh JU, Hwang M, Cho HW, Bae JH, et al. Orexin A-induced inhibition of leptin expression and secretion in adipocytes reducing plasma leptin levels and hypothalamic leptin resistance. Pflugers Arch. 2019;471(11-12):1407–18.
  • Kusakabe T, Ebihara K, Sakai T, Miyamoto L, Aotani D, Yamamoto Y, et al. Amylin improves the effect of leptin on insulin sensitivity in leptin-resistant diet-induced obese mice. Am J Physiol Endocrinol Metab. 2012;302(8):E924–931.
  • Moon HS, Matarese G, Brennan AM, Chamberland JP, Liu X, Fiorenza CG, et al. Efficacy of metreleptin in obese patients with type 2 diabetes: cellular and molecular pathways underlying leptin tolerance. Diabetes. 2011;60(6):1647–56.
  • Trevaskis JL, Meyer EA, Galgani JE, Butler AA. Counterintuitive effects of double-heterozygous null melanocortin-4 receptor and leptin genes on diet-induced obesity and insulin resistance in C57BL/6J mice. Endocrinology. 2008;149(1):174–84.
  • Donnelly JE, Hill JO, Jacobsen DJ, Potteiger J, Sullivan DK, Johnson SL, et al. Effects of a 16-month randomized controlled exercise trial on body weight and composition in young, overweight Men and women. Arch Intern Med. 2003;163(11):1343–50.
  • Johnstone AM, Murison SD, Duncan JS, Rance KA, Speakman JR. Factors influencing variation in basal metabolic rate include fat-free mass, fat mass, age, and circulating thyroxine but not sex, circulating leptin, or triiodothyronine. Am J Clin Nutr. 2005;82(5):941–8.
  • Pelleymounter MA, Cullen MJ, Baker MB, Hecht R, Winters D, Boone T, et al. Effects of the obese gene product on body weight regulation in ob/ob mice. Science. 1995;269(5223):540–3.
  • Chan JL, Heist K, DePaoli AM, Veldhuis JD, Mantzoros CS. The role of falling leptin levels in the neuroendocrine and metabolic adaptation to short-term starvation in healthy men. J Clin Invest. 2003;111(9):1409–21. doi:10.1172/jci17490.
  • Chrysafi P, Perakakis N, Farr OM, Stefanakis K, Peradze N, Sala-Vila A, et al. Leptin alters energy intake and fat mass but not energy expenditure in lean subjects. Nat Commun. 2020;11(1):5145.
  • Ropelle ER, Flores MB, Cintra DE, Rocha GZ, Pauli JR, Morari J, et al. IL-6 and IL-10 anti-inflammatory activity links exercise to hypothalamic insulin and leptin sensitivity through IKKbeta and ER stress inhibition. PLoS Biol. 2010;8(8).
  • Dodd GT, Decherf S, Loh K, Simonds SE, Wiede F, Balland E, et al. Leptin and insulin Act on POMC neurons to promote the browning of white Fat. Cell. 2015;160(1):88–104.
  • Rosenbaum M, Leibel R. Role of leptin in energy homeostasis in humans. J Endocrinol. 2014;223(1):T83–T96.
  • Mittendorfer B, Horowitz JF, DePaoli AM, McCamish MA, Patterson BW, Klein S. Recombinant human leptin treatment does not improve insulin action in obese subjects with type 2 diabetes. Diabetes. 2011;60(5):1474–7.
  • Mackintosh RM, Hirsch J. The effects of leptin administration in non-obese human subjects. Obesity Res. 2001;9(8):462–9.
  • Hukshorn CJ, Saris WH, 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. 2000;85(11):4003–9.
  • Shetty GK, Matarese G, Magkos F, Moon H-S, Liu X, Brennan AM, et al. Leptin administration to overweight and obese subjects for 6 months increases free leptin concentrations but does not alter circulating hormones of the thyroid and IGF axes during weight loss induced by a mild hypocaloric diet. Eur J Endocrinol. 2011;165(2):249–54.
  • Zelissen PM, Stenlof K, Lean ME, Fogteloo J, Keulen ET, Wilding J, et al. Effect of three treatment schedules of recombinant methionyl human leptin on body weight in obese adults: a randomized, placebo-controlled trial. Diab Obesity Metab. 2005;7(6):755–61.
  • Heymsfield SB, Greenberg AS, Fujioka K, Dixon RM, Kushner R, Hunt T, et al. Recombinant leptin for weight loss in obese and lean adults. JAMA. 1999;282(16):1568–75.
  • Fogteloo AJ, Pijl H, Frölich M, McCamish M, Meinders AE. Effects of recombinant human leptin treatment as an adjunct of moderate energy restriction on body weight, resting energy expenditure and energy intake in obese humans. Diab Nutr Metab. 2003;16(2):109–14.
  • Rosenbaum M, Goldsmith R, Bloomfield D, Magnano A, Weimer L, Heymsfield S, et al. Low-dose leptin reverses skeletal muscle, autonomic, and neuroendocrine adaptations to maintenance of reduced weight. J Clin Investig. 2005;115(12):3579–86.
  • Knuth ND, Johannsen DL, Tamboli RA, Marks-Shulman PA, Huizenga R, Chen KY, et al. Metabolic adaptation following massive weight loss is related to the degree of energy imbalance and changes in circulating leptin. Obesity (Silver Spring). 2014;22(12):2563–9.

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.