Weight Displacement Activity

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Science  15 Oct 2004:
Vol. 306, Issue 5695, pp. 377
DOI: 10.1126/science.306.5695.377c

As all dieters know, the key to weight loss is altering the balance between energy intake and energy expenditure. At the molecular level, one of the major regulators of energy balance is PGC-1α, a nuclear protein that stimulates the transcription of genes involved in diverse metabolic processes such as glucose production in the liver and mitochondrial function in fat and muscle.

A new study of PGC-1α-deficient mice by Lin et al. confirms the protein's central role in metabolic control but also reveals some surprises. Rather than being prone to weight gain, as predicted by earlier cell culture studies, the mutant mice stayed lean, even when on a high-fat diet. This effect was due, at least in part, to increased energy expenditure: Mice lacking PGC-1α were profoundly hyperactive, showing a 40% increase in random movements as compared to control mice. The mutant mice also showed behavioral disturbances and had brain lesions reminiscent of those seen in certain neurodegenerative disorders, such as Huntington's disease. Interestingly, these brain disorders have been linked previously to defects in mitochondria, whose function is known to be regulated by PGC-1α in other tissue types. — PAK

Cell 119, 121 (2004).

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