Leptin and Congenital Leptin Deficiency

Congenital leptin deficiency due to mutations in the leptin gene or receptor is a rare, but treatable, cause of severe early-onset obesity and various endocrine disturbances in both rodents and humans [74, 75]. According to the lypostatic theory, a state of 'perceived starvation' might exist in these subjects and results in a chronic stimulation of excessive food intake [39]. Leptin therapy has shown to have dramatically beneficial effects on weight, fat mass and appetite, hyperinsulinaemia and lipid levels, as well as on neuroendocrine phe-notypes and immune functions in these subjects [76, 77]. Leptin treatment blunts the changes in circulating thyroid hormone and corticosterone levels that are normally associated with food deprivation. It has been suggested that the inhibition of thyroid hormone secretion may have evolved to limit energy expenditure and prevent protein catabolism during starvation [78]. The effect of leptin on circulating thyroid hormone can be explained at least in part by the high expression of leptin receptor in the arcuate nucleus of the hypothalamus and by the known projection of the arcuate nucleus to the paraventricular nucleus, where the thyroid-releasing hormone neurons are localised [79].

Total leptin deficiency or insensitivity is associated with hypothalamic hypogonadism in humans and rodents. Leptin treatment restored luteinising hormone secretion and pubertal development in leptin-deficient patients, confirming its critical role in reproduction. It was proposed that high levels of leptin observed in children might reflect leptin resistance, as seen in obesity, serving to maintain sufficient food intake and growth and prevent the onset of premature puberty. Central leptin administration decreases the expression of

NPY in the hypothalamus and consequently removes the inhibitory action of NPY on growth hormone-releasing hormone (GHRH) release. Leptin stimulates the synthesis and release of luteinising hormone and follicle-stimulating hormone in animals. Ovarian follicular cells are regulated directly by leptin, indicating that it is able to control the hypothalamic-pituitary-gonadal axis at multiple levels [79, 80]. These results show that leptin is not only an adipostat signal, but it acts as a metabolic switch, informing the brain when fat reserves are adequate to direct energy expenditure towards activities other than seeking calories [37].

Supplements For Diabetics

Supplements For Diabetics

All you need is a proper diet of fresh fruits and vegetables and get plenty of exercise and you'll be fine. Ever heard those words from your doctor? If that's all heshe recommends then you're missing out an important ingredient for health that he's not telling you. Fact is that you can adhere to the strictest diet, watch everything you eat and get the exercise of amarathon runner and still come down with diabetic complications. Diet, exercise and standard drug treatments simply aren't enough to help keep your diabetes under control.

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