Molecular disruption of hypothalamic nutrient sensing induces obesity
- 15 January 2006
- journal article
- research article
- Published by Springer Science and Business Media LLC in Nature Neuroscience
- Vol. 9 (2), 227-233
- https://doi.org/10.1038/nn1626
Abstract
The sensing of circulating nutrients within the mediobasal hypothalamus may be critical for energy homeostasis. To induce a sustained impairment in hypothalamic nutrient sensing, adeno-associated viruses (AAV) expressing malonyl–coenzyme A decarboxylase (MCD; an enzyme involved in the degradation of malonyl coenzyme A) were injected bilaterally into the mediobasal hypothalamus of rats. MCD overexpression led to decreased abundance of long-chain fatty acyl–coenzyme A in the mediobasal hypothalamus and blunted the hypothalamic responses to increased lipid availability. The enhanced expression of MCD within this hypothalamic region induced a rapid increase in food intake and progressive weight gain. Obesity was sustained for at least 4 months and occurred despite increased plasma concentrations of leptin and insulin. These findings indicate that nutritional modulation of the hypothalamic abundance of malonyl–coenzyme A is required to restrain food intake and that a primary impairment in this central nutrient-sensing pathway is sufficient to disrupt energy homeostasis and induce obesity.This publication has 31 references indexed in Scilit:
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