B-Bridge - Adipokine ELISAs, Leptin - the Product of the ob Gene

ELISAs

Adipokine ELISAs

Adiponectin

Leptin

- Leptin
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Leptin Receptor

Resistin

Leptin - the Product of the ob Gene

Leptin, the product of the ob (obese) gene, is a single-chain 16 kDa protein consisting of 146 amino acid residues. Leptin is produced mainly in the adipose tissue, and is considered to play an important role in appetite control, fat metabolism and body weight regulation. It targets the central nervous system, particularly the hypothalamus, which affects food intake. The primary effect of leptin appears to be mediated by leptin receptors expressed mainly in the hypothalamus. In humans, leptin levels correlate with body mass index (BMI) and percentage body fat, and are elevated in obese individuals. Leptin has a dual action; it decreases the appetite and increases energy consumption, causing more fat to be burned. Leptin is secreted in circadian fashion with nocturnal rise in both lean and obese patients. Mutations of the ob gene resulting in a leptin deficiency are the cause of obesity in the ob/ob mice. Endogeneous leptin can normalize their body weight. In contrast, high levels of leptin in obese human subjects point to an insensitivity to endogeneous leptin. Other factors in addition to the amount of body fat appear to regulate leptin action: insulin, glucocorticoids, catecholamines and sex hormones. Studies have shown that leptin may be linked to reproductive function.

References for Leptin:

Auwerx J. and Staels B.: Leptin (Review article). The Lancet 13, 737 (1998)

Blum W.F., Englaro P., Hanitsch S. et al.: Plasma leptin levels in healthy children and adolescents: Dependence on body mass index, body fat mass, gender, pubertal stage, and testosterone. J. Clin. Endocrinol. Metab. 82, 2904 (1997)

Cohen B., Novick D. and Rubinstein M.: Modulation of insulin activities by leptin. Science 274, 1185 (1996)

Considine R.V., Sinha M.K., Heiman M.L., Kriaciunas A., Stephens T.W., Nyce M.R., Ohannesian J.P., Marco C.C., McKee L.J., Bauer T.L. and Caro J.F.: Serum immunoreactive leptin concentrations in normal-weight and obese humans. N. Engl. J. Med. 334, 292-295 (1996)

Halaas J.L., Gajiwala K.S., Maffei M., Cohen S.L., Chait B.T., Rabinowitz D., Lallone R.L., Burley S.K. and Friedman J.M.: Weight-reducing effects of the plasma protein encoded by the obese gene. Science 269, 543-546 (1995)

Harigaya A., Nagashima K., Nako Y. and Marikawa A.: Relationship between concentration of serum leptin and fetal growth. J. Clin. Endocrinol. Metab. 82, 3281 (1997)

Lönnqvist F., Arner P., Nordfors L. and Shalling M.: Overexpression of the obese (ob) gene in adipose tissue of human subjects. Nature Med. 1, 950-953 (1995)

Maffei M., Halaas J., Ravussin E., Pratley R.E., Lee G.H., Zhang Y., Fei H., Kim S., Lallone R., Ranganathan S., Kern P.A. and Friedman J.M.: Leptin levels in human and rodent: measurement of plasma leptin and ob RNA in obese and weightreduced subjects. Nature Med. 1, 1155-1161 (1995)

Pelleymounter M.A., Cullen M.J., Baker M.B., Hecht R., Winters D., Boone T. and Collins F.: Effects of the obese gene product on body weight regulation in ob/ob mice. Science 269, 540-543 (1995)

Spiegelman B.M., Flier J.S.: Adipogenesis and obesity: Rounding out the big picture, Cell 87, 377- 389 (1996)

Tartaglia L.A.: The leptin receptor, J. Biol. Chem. 272, 6093-6096 (1997)

Tritos N.A., Mantzoros C.S.: Leptin: its role in obesity and beyond, Diabetologia 40, 1371-1379 (1997)

Zhang F., Basinski M. B., Beals J.M., Briggs S.L., Churgay L.M., Clawson D.K., DiMarchi R.D., Furman T.C., Hale J.E., Hsiung H.M., Schoner B.E., Smith D.P., Zhang X.Y., Wery J.P., and Schevitz R.W.: Crystal structure of the obese protein leptin- E100, Nature 387, 206-209 (1997)

Zhang Y., Proenca R., Maffei M., Barone M., Leopold L., Friedman J.M.: Positional cloning of the mouse obese gene and its human homologue. Nature 372, 425-432 (1994)