Body fat has complex control mechanisms regulated by a hypothalamic lipostatic feedback system. Lipid metabolism in selective hypothalamic neurons may be a primary biochemical sensor for nutrient availability, but the molecular mechanisms involved have been unclear. In the May 19 advanced online Nature Medicine, Silvana Obici and colleagues at the Albert Einstein College of Medicine show that inhibition of hypothalamic carnitine palmitoyltransferase-1 (CPT1) decreases food intake and glucose production (Nature Medicine, DOI:10.1038/nm873, May 18, 2003).

CPT1 controls the import of long-chain fatty acids into the mitochondria, where they are oxidized. Using rats, Obici et al. selectively decreased the activity of CPT1 by administering a ribozyme-containing plasmid designed to decrease the expression of CPT1 or by injecting CPT1 inhibitors into the third cerebral ventricle. They observed that after either genetic or biochemical inhibition of hypothalamic CPT1, the food intake of these animals and endogenous glucose production diminished.


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