Leptin

A hormone involved in the regulation of body fat. Leptin was originally thought to be a signal to lose weight but it may instead be a way for the brain to know that there is fat on the body. A few hugely obese children have been found who have an inability to lose weight due to a genetic inability to produce leptin. Injections of leptin have had dramatic weight loss effects. It appears that, if one cannot make leptin, the brain thinks there is no fat and spurs the person on to eat more and more in a futile effort to get the leptin signal that fat is present. However, the effect of leptin on people who are obese but make leptin appears to be different. A study of leptin published in the Journal of the American Medical Association (JAMA) in 1999 returned somewhat disappointing results. It involved 54 people of normal weight and 73 who were obese. All injected themselves daily with leptin or, as a control, with saline (saltwater) for a month. Then the study continued with the obese subjects to assess leptin's ability to induce weight loss. The obese patients were given a weight-loss diet. There was little effect of leptin except at the highest dose tested, when 2 of 8 patients lost about 35 pounds in 24 weeks. The others lost much less and one gained weight. The 8 people on the highest dose of leptin were the last of a group of 18 patients who had been assigned to take it; the rest dropped out after a month of taking leptin because they could not stand to inject themselves with several tablespoons a day of a substance that irritated their skin and was painful to administer. The future of leptin in weight regulation remains to be determined.

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A helical protein secreted by adipose tissue and acting on a receptor site in the ventromedial nucleus of the hypothalamus to curb appetite and increase energy expenditure as body fat stores increase. L. levels are 40% higher in women, and show a further 50% rise just before menarche, later returning to baseline levels; levels are lowered by fasting and increased by inflammation. [G. leptos, thin, + -in] Human genes encoding both l. (locus 7q31.3) and the l. receptor site (1p31) have been identified. Laboratory mice having mutations on the ob gene, which encodes l., become morbidly obese, diabetic, and infertile; administration of l. to these mice improves glucose tolerance, increases physical activity, reduces body weight by 30%, and restores fertility. Mice with mutations of the db gene, which encodes the l. receptor, also become obese and diabetic but do not improve with administration of l.. Although mutations in both the l. and l. receptor genes have been found in a small number of morbidly obese human subjects with abnormal eating behavior, the majority of obese persons do not show such mutations, and have normal or elevated circulating levels of l.. L. enhances insulin-mediated glucose transport into adipose cells in vitro. In preliminary trials, both lean and overweight persons have shown modest weight loss with daily subcutaneous injections of recombinant methionyl human l. over several months. All subjects followed weight-reduction diets during the trial period. Weight loss in some subjects receiving l. did not exceed that achieved by subjects receiving placebo, but when significant weight reduction occurred, it was proportionate to dosage. The immune deficiency seen in starvation may result from diminished l. secretion. Mice lacking the gene for l. or its receptor show impairment of T-cell function, and in laboratory studies l. has induced a proliferative response in human CD4 lymphocytes.

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lep·tin 'lep-tən n a peptide hormone that is produced by fat cells and plays a role in body weight regulation by acting on the hypothalamus to suppress appetite and burn fat stored in adipose tissue

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n.

a protein, produced by white fat cells in adipose tissue, that is involved in controlling the amount of white adipose tissue laid down in the body. It acts on the brain, possibly as a signal to regulate appetite or energy expenditure. Mutations in the ob gene, which codes for leptin, are responsible for some cases of obesity.

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lep·tin (lepґtin) a 167 amino acid adipocytokine that is part of a feedback loop that provides information to the brain about the state of nutrient stores. After secretion, it circulates in plasma and interacts with a specific receptor in the hypothalamus, decreasing food intake and increasing energy expenditure. It also increases insulin sensitivity, which is believed to result partly from its effect on the hypothalamus and partly from its action on peripheral tissues.