germ-free = no obesity

Proc Natl Acad Sci U S A. 2007 Jan 8;
[Epub ahead of print]
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Mechanisms underlying the resistance to diet-induced obesity in
germ-free mice.

Backhed F, Manchester JK, Semenkovich CF, Gordon JI.

Center for Genome Sciences and Department of Medicine,
Washington University School of Medicine,
St. Louis, MO
63108.


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.


PMID: 17210919 [PubMed - as supplied by publisher]