Backhed F, Manchester JK, Semenkovich CF, Gordon JI.. Mechanisms underlying the resistance to diet-induced obesity in germ-free mice. Proc Natl Acad Sci USA 104: 979-984

Washington University in St. Louis, San Luis, Missouri, United States
Proceedings of the National Academy of Sciences (Impact Factor: 9.67). 02/2007; 104(3):979-84. DOI: 10.1073/pnas.0605374104
Source: PubMed


The trillions of microbes that colonize our adult intestines function collectively as a metabolic organ that communicates with, and complements, our own human metabolic apparatus. Given the worldwide epidemic in obesity, there is interest in how interactions between human and microbial metabolomes may affect our energy balance. Here we report that, in contrast to mice with a gut microbiota, germ-free (GF) animals are protected against the obesity that develops after consuming a Western-style, high-fat, sugar-rich diet. Their persistently lean phenotype is associated with increased skeletal muscle and liver levels of phosphorylated AMP-activated protein kinase (AMPK) and its downstream targets involved in fatty acid oxidation (acetylCoA carboxylase; carnitine-palmitoyltransferase). Moreover, GF knockout mice lacking fasting-induced adipose factor (Fiaf), a circulating lipoprotein lipase inhibitor whose expression is normally selectively suppressed in the gut epithelium by the microbiota, are not protected from diet-induced obesity. Although GF Fiaf-/- animals exhibit similar levels of phosphorylated AMPK as their wild-type littermates in liver and gastrocnemius muscle, they have reduced expression of genes encoding the peroxisomal proliferator-activated receptor coactivator (Pgc-1alpha) and enzymes involved in fatty acid oxidation. Thus, GF animals are protected from diet-induced obesity by two complementary but independent mechanisms that result in increased fatty acid metabolism: (i) elevated levels of Fiaf, which induces Pgc-1alpha; and (ii) increased AMPK activity. Together, these findings support the notion that the gut microbiota can influence both sides of the energy balance equation, and underscore the importance of considering our metabolome in a supraorganismal context.

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    • "The lack of standardized methods represents the main limiting factor. These experiments differ not only in diet composition (Backhed et al., 2007 used WD while Fleissner et al., 2010 "
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    • "Particularly, the gut microbiota can control fatty-acid oxidation in the host via suppression of the AMPactivated protein kinases (AMPKs). By contrast, the gut microbiota can also induce fat storage in the host by suppression of fastinginduced adipose factor (Fiaf) (Bäckhed et al., 2007). These results are valuable in understanding the pathology of obesity because they determine the inside mechanisms of how gut microbiota can contribute to energy balance of the host. "
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