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Science  27 May 2005:
Vol. 308, Issue 5726, pp. 1227b
DOI: 10.1126/science.308.5726.1227b

Pursuing good health may mean including enough fat in your diet. Fat that is either consumed or synthesized de novo in cells is considered new, whereas old fat is stored in adipose tissue, waiting to be used. According to Chakravarthy et al., the liver discriminates between these sources as it coordinates nutrient and energy homeostasis.

Fatty acids serve as the natural ligands for PPARα, a hepatocyte nuclear receptor that regulates genes involved in the metabolism of glucose, fatty acids, and cholesterol. When fed a diet with no fat, mice lacking fatty acid synthase (FAS) developed hypoglycemia due to a failure in activating target genes of PPARα that control gluconeogenesis (GNEO). Paradoxically, the livers in these mice became fat-laden because of the mobilization of peripheral fat and the inability of the livers to express PPARα target genes involved in fatty acid oxidation (FAO). Adding dietary fat or an agonist of PPARα reversed these symptoms. Mice lacking FAS also had low serum and liver cholesterol levels due to decreased hepatic cholesterol synthesis (CHOL). The authors propose that new fat may activate a distinct pool of PPARα in the liver to maintain normal levels of glucose, fat and cholesterol. Metabolic abnormalities associated with obesity and diabetes might be treated by pharmacologically activating these distinct receptor pools. — LDC

Cell Metab. 1, 309 (2005).

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