Leptin mouse brain

Kokkotou, E. G., Tiitos, N. A., Mastaitis, J. W., Slieker, L., and Maratos-Flier, E. (2001) Melanin-concentrating hormone receptor is a target of leptin action in the mouse brain. Endocrinology. 142, 680-686. 

Maness LM, Kastin AJ, EarreU CL, Banks WA (1998) Fate of leptin after intracerebroventricular injection into the mouse brain. Endocrinology 139 4556-4562. 

Leptin is a cytokine produced and secreted by adipose tissue in proportion to the body fat content [3]. Mice and humans lacking leptin or its receptor develop a severe hyperphagia and a dramatic degree of obesity which is considerably more pronounced than that of the NDRKO mouse. Thus, leptin is the key adiposity signal in rodents and humans. Leptin secretion appears to reflect the metabolic status of the adipocyte rather than the sheer size of triglyceride deposits, and leptin levels may transiently be dissociated from total body fat. Nonetheless, over the course of a day with unrestricted food supply, plasma leptin levels reliably reflect the amount of total body fat. Local administration of leptin into the brain results in reduced food intake. The vast majority of patients with obesity have elevated serum levels of leptin. Thus, it is believed that the polygenic obesity is due to leptin resistance rather than to inadequate leptin secretion, or to a reduced blood/brain transport of the cytokine. 

The increase in neuropeptide Y results in an increase in food intake. Obesity in the normal mouse results in an increase in plasma leptin, where increased levels of leptin at the leptin receptor (in the hypothalamus) provokes an increase in melanocortin (MSH). The increase in MSH in the brain pnjvokes an increase in stimulation of the melanocortin-4 receptor in the brain, which results in a decline in food intake- MSH is the hormone that binds to melanocortin receptors, where this interaction can be antagonized if agouti protein is allowed to contact the receptor. 

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