The gut microbiota as an environmental factor that regulates fat storage.
New therapeutic targets for noncognitive reductions in energy intake, absorption, or storage are crucial given the worldwide epidemic of obesity. The gut microbial community (microbiota) is essential for processing dietary polysaccharides. We found that conventionalization of adult germ-free (GF) C57BL/6 mice with a normal microbiota harvested from the distal intestine (cecum) of conventionally raised animals produces a 60% increase in body fat content and insulin resistance within 14 days despite reduced food intake. Studies of GF and conventionalized mice revealed that the microbiota promotes absorption of monosaccharides from the gut lumen, with resulting induction of de novo hepatic lipogenesis. Fasting-induced adipocyte factor (Fiaf), a member of the angiopoietin-like family of proteins, is selectively suppressed in the intestinal epithelium of normal mice by conventionalization. Analysis of GF and conventionalized, normal and Fiaf knockout mice established that Fiaf is a circulating lipoprotein lipase inhibitor and that its suppression is essential for the microbiota-induced deposition of triglycerides in adipocytes. Studies of Rag1-/- animals indicate that these host responses do not require mature lymphocytes. Our findings suggest that the gut microbiota is an important environmental factor that affects energy harvest from the diet and energy storage in the host. Data deposition: The sequences reported in this paper have been deposited in the GenBank database (accession nos. AY 667702--AY 668946).
Bäckhed
Fredrik
F
Center for Genome Sciences and Department of Molecular Biology and Pharmacology, Washington University School of Medicine, St. Louis, MO 63110, USA.
Ding
Hao
H
Wang
Ting
T
Hooper
Lora V
LV
Koh
Gou Young
GY
Nagy
Andras
A
Semenkovich
Clay F
CF
Gordon
Jeffrey I
JI
D017667:Adipocytes / Q000378:metabolism; D000273:Adipose Tissue / Q000033:anatomy & histology / Q000378:metabolism; D000075803:Angiopoietin-Like Protein 4; D042682:Angiopoietins; D000818:Animals; D001798:Blood Proteins / Q000172:deficiency / Q000235:genetics / Q000378:metabolism; D004041:Dietary Fats / Q000378:metabolism*; D004064:Digestive System / Q000378:metabolism* / Q000382:microbiology*; D004734:Energy Metabolism; D005856:Germ-Free Life; D006801:Humans; D007333:Insulin Resistance / Q000502:physiology; D008071:Lipoprotein Lipase / Q000037:antagonists & inhibitors; D008099:Liver / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008954:Models, Biological; D008969:Molecular Sequence Data; D009765:Obesity / Q000209:etiology; D014280:Triglycerides / Q000096:biosynthesis
D000075803:Angiopoietin-Like Protein 4; D042682:Angiopoietins; C407088:Angptl4 protein, mouse; D001798:Blood Proteins; D004041:Dietary Fats; D014280:Triglycerides; D008071:Lipoprotein Lipase