The Somatotrope as a Metabolic Sensor: Deletion of Leptin Receptors Causes Obesity
Endocrinology, 11/18/2010Childs GV et al.
Leptin, the product of the Lep gene, reports levels of adiposity to the hypothalamus and other regulatory cells, including pituitary somatotropes, which secrete GH. Leptin deficiency is associated with a decline in somatotrope numbers and function, suggesting that leptin may be important in their maintenance. Organ genotyping confirmed the recombination of the floxed LepR allele only in the pituitary.
Gwen V. Childs (11/28/2010)
This study was originally designed to test the hypothesis that leptin signals to growth hormone cells are important to the timing of puberty. We selectively ablated the gene for leptin receptor on growth hormone cells with Cre-LoxP technology. The genetically altered mice grew normally, in spite of the fact that their growth hormone levels were reduced. They had a 60% reduction in numbers of growth hormone cells. However, they entered puberty within the normal time frame and were able to reproduce. Some of the mutant females had fewer pups/litter, however.
The striking change came when the males were 3.5-5 months old. They became obese, with steady increase in fat mass until they were over a year old. In females, the obesity was seen later (6 months of age), however it progressed rapidly after that. DEXA analysis showed that the weight gain was due to increased fat mass. Future studies will focus on the metabolic factors leading to the weight gain.
These studies show the importance of leptin signals to growth hormone cells and suggest that growth hormone plays a role as a critical metabolic sensor, allowing it to regulate fat stores. If growth hormone cells can't receive the leptin (in our mutant mice), they can't do their job, to regulate adiposity.
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