/lp/springer-journals/molecular-disruption-of-hypothalamic-nutrient-sensing-induces-obesity-aypun0gQVr
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- Publisher
- Springer Journals
- Copyright
- Copyright © 2006 by Nature Publishing Group
- Subject
- Biomedicine; Biomedicine, general; Neurosciences; Behavioral Sciences; Biological Techniques; Neurobiology; Animal Genetics and Genomics
- ISSN
- 1097-6256
- eISSN
- 1546-1726
- DOI
- 10.1038/nn1626
- Publisher site
- See Article on Publisher Site
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.
Journal
Nature Neuroscience – Springer Journals
Published: Jan 15, 2006