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      The role of falling leptin levels in the neuroendocrine and metabolic adaptation to short-term starvation in healthy men

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          Most cited references 43

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          A mutation in the human leptin receptor gene causes obesity and pituitary dysfunction.

          The adipocyte-specific hormone leptin, the product of the obese (ob) gene, regulates adipose-tissue mass through hypothalamic effects on satiety and energy expenditure. Leptin acts through the leptin receptor, a single-transmembrane-domain receptor of the cytokine-receptor family. In rodents, homozygous mutations in genes encoding leptin or the leptin receptor cause early-onset morbid obesity, hyperphagia and reduced energy expenditure. These rodents also show hypercortisolaemia, alterations in glucose homeostasis, dyslipidaemia, and infertility due to hypogonadotropic hypogonadisms. In humans, leptin deficiency due to a mutation in the leptin gene is associated with early-onset obesity. Here we describe a homozygous mutation in the human leptin receptor gene that results in a truncated leptin receptor lacking both the transmembrane and the intracellular domains. In addition to their early-onset morbid obesity, patients homozygous for this mutation have no pubertal development and their secretion of growth hormone and thyrotropin is reduced. These results indicate that leptin is an important physiological regulator of several endocrine functions in humans.
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            A leptin missense mutation associated with hypogonadism and morbid obesity.

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              Beneficial effects of leptin on obesity, T cell hyporesponsiveness, and neuroendocrine/metabolic dysfunction of human congenital leptin deficiency

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                Author and article information

                Journal
                Journal of Clinical Investigation
                J. Clin. Invest.
                American Society for Clinical Investigation
                0021-9738
                May 1 2003
                May 1 2003
                : 111
                : 9
                : 1409-1421
                Article
                10.1172/JCI200317490
                © 2003
                Product
                Self URI (article page): http://www.jci.org/articles/view/17490

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