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Gut Microbes Make Fat Mice

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Science's STKE  09 Nov 2004:
Vol. 2004, Issue 258, pp. tw404
DOI: 10.1126/stke.2582004tw404

The mammalian gut has many microorganisms that allow the processing of otherwise indigestible food components; these organisms are called the gut microbiota. Bäckhed et al. report that colonization of mice that lack any endogenous microbiota (GF mice) with a single strain of bacteria promoted weight gain, fat storage, and altered metabolism. This process of introducing microbiota is called conventionalization. The conventionalized mice also showed increased concentrations of circulating leptin, a hormone that reduces food intake and increases energy expenditure, compared with the GF mice. Indeed, the conventionalized mice ate less but still were fatter and heavier than GF mice were. The conventionalized mice had increased production of triglycerides in the liver due to increased expression of Fas and Acc1 genes that encode two key enzymes in fatty acid biosynthesis. The activity and abundance of carbohydrate response element binding protein (ChREBP) and to a lesser extent sterol response element binding protein 1 (SREBP-1), which coordinately stimulate Acc1 and Fas expression, were increased in the conventionalized mice. The abundance of lipoprotein lipase (LPL) is an important regulator of triglyceride storage in various tissues, including adipocytes. Fat pads of conventionalized mice had increased activity of LPL. Fiaf is a circulating inhibitor of LPL, and the expression of Fiaf was inhibited in the small intestine of conventionalized mice. GF mice that were deficient in Fiaf did not show changes in fat pad LPL activity and had only modest increases in body fat following conventionalization. Thus, gut microbiota not only allow the indigestible food products to be digested but also provide signals that regulate lipid storage and hepatic lipogenesis.

F. Bäckhed, H. Ding, T. Wang, L. V. Hooper, G. Y. Koh, A. Nagy, C. F. Semenkovich, J. I. Gordon, The gut microbiota as an environmental factor that regulates fat storage. Proc. Natl. Acad. Sci. U.S.A. 101, 15718-15723 (2004). [Abstract] [Full Text]

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