Hamdan Medical Journal (previously the Journal of Medical Sciences)

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Leptin and the Regulation of Body Weight

Jeffrey M.D Friedman
Published in : Journal of Medical Sciences ; Vol 3, No 3 (2010)
DOI : 10.2174/1996327001003030131


The discovery of leptin has led to the elucidation of a robust physiologic system that maintains fat stores at a relatively constant level. Leptin is a peptide hormone secreted by adipose tissue in proportion to its mass. This hormone circulates in blood and acts on the hypothalamus to regulate food intake and energy expenditure. When fat mass falls, plasma leptin levels fall stimulating appetite and suppressing energy expenditure until fat mass is restored. When fat mass increases, leptin levels increase, suppressing appetite until weight is lost. By such a mechanism total energy stores are stably maintained within a relatively narrow range.

Recessive mutations in the leptin gene are associated with massive obesity in mice and some humans. Treatment with recombinant leptin markedly reduces food intake and body weight. The low leptin levels in patients with leptin mutations are also associated with multiple abnormalities including infertility, diabetes and immune abnormalities all of which are corrected by leptin treatment. These findings have established important links between energy stores and many other physiologic systems and led to the use of leptin as a treatment for an increasing number of other human conditions including a subset of obesity, some forms of diabetes including lipodystrophy and hypothalamic amennorhea, the cessation of menstruation seen in extremely thin women. Identification of a physiologic system that controls energy balance establishes a biologic basis for obesity and further establishes links between leptin and numerous other physiologic responses.


Obesity; leptin; diabetes; infertility; homeostasis

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Bray GA. Obesity: Historical development of scientific and cultural ideas. Int J Obes 1990; 14: 909-26.

Coleman DL. Effects of parabiosis of obese with diabetes and normal mice. Diabetologia 1973; 9: 294-8.

Zhang Y, Proenca R, Maffei M, Barone M, Leopold L, Friedman JM. Positional cloning of the mouse obese gene and its human homologue. Nature 1994; 372: 425-32.

Halaas JL, Gajiwala KS, Maffei M, Cohen SL, Chait BT, Rabinowitz D, et al. Weight-reducing effects of the plasma protein encoded by the obese gene. Science 1995; 269: 543-6.

Moon BC, Friedman JM. The molecular basis of the obese mutation in ob2J mice. Genomics 1997; 42: 152-6.

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: 540-3.

Campfield LA,Smith FJ, Guisez Y, Devos R, Burn P. Recombinant mouse OB protein: Evidence for a peripheral signal linking adiposity and central neural networks. Science 1995; 269: 546-9.

Maffei M, Halaas J, Ravussin E, Pratley RE, Lee GH, Zhang Y, et al. Leptin levels in human and rodent: Measurement of plasma leptin and ob RNA in obese and weight-reduced subjects. Nat Med 1995; 1: 1155-61.

Halaas JL, Boozer C, Blair-West J, Fidahusein N, Denton DA, Friedman JM. Physiological response to long-term peripheral and central leptin infusion in lean and obese mice. Proc Natl Acad Sci USA 1997; 94: 8878-83.

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: 1263-71.

Lee GH, Proenca R, Montez JM, Carroll KM, Darvishzadeh JG, Lee JI, et al. Abnormal splicing of the leptin receptor in diabetic mice. Nature 1996; 379: 632-5.

Chen H, Charlat O, Tartaglia LA, Woolf EA, Weng X, Ellis SJ, et al. Evidence that the diabetes gene encodes the leptin receptor: Identification of a mutation in the leptin receptor gene in db/db mice. Cell 1996; 84: 491-5.

Fei H, Okano HJ, Li C, Lee GH, Zhao C, Darnell R, et al. Anatomic localization of alternatively spliced leptin receptors (Ob-R) in mouse brain and other tissues. Prod Natl Acad Sci USA 1997; 94: 7001-5.

Farooqi IS, Jebb SA, Langmack G, Lawrence E, Cheetham CH, Prentice AM, et al. Effects of recombinant leptin theraphy in a child with congenital leptin deficiency. N Engl J Med. 1999; 341: 879-84.

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: 1568-75.

Ioffe E,Moon B, Connolly E, Friedman JM. Abnormal regulation of the leptin gene in the pathogenesis of obesity. Proc Natl Acad Sci USA 1998; 95: 11852-7.

Roth JD, Roland BL, Cole RL, Trevaskis JL, Weyer C, Koda JE, et al. Leptin responsiveness restored by amylin agonism in diet-induced obesity: evidence from nonclinical and clinical studies. Proc Natl Acad Sci 2008; 105: 7257-62.

Friedman JM. Modern science versus the stigma of obesity. Nat Med 2004; 10: 563-9.

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