gut microbiota as an environmental factor that regulates fat storage

• Published in: Proceedings of the National Academy of Sciences - PNAS 2004-11, Vol.101 (44), p.15718-15723
• Main Authors: Backhed, F, Ding, H, Wang, T, Hooper, L.V, Koh, G.Y, Nagy, A, Semenkovich, C.F, Gordon, J.I
• Format: Article
• Language: English
• Subjects: Adipocytes; Adipocytes - metabolism; Adipose Tissue - anatomy & histology; Adipose Tissue - metabolism; Adipose tissues; Angiopoietin-Like Protein 4; Angiopoietins; Animals; Biological Sciences; Blood Proteins - deficiency; Blood Proteins - genetics; Blood Proteins - metabolism; Body fat; cecum; Dietary Fats - metabolism; Digestive System - metabolism; Digestive System - microbiology; Energy; Energy Metabolism; enzyme inhibitors; Fasting; fasting-induced adipose factor; germ-free animals; Germ-Free Life; Humans; Insulin; Insulin Resistance - physiology; intestinal absorption; intestinal microorganisms; Intestines; lipogenesis; lipoprotein lipase; Lipoprotein Lipase - antagonists & inhibitors; Liver; Liver - metabolism; Male; Mice; Mice, Inbred C57BL; Mice, Knockout; Microbiota; Models, Biological; Molecular Sequence Data; monosaccharides; mutants; nucleotide sequences; Nutrition; Obesity - etiology; Oxygen consumption; ribosomal DNA; Storage; Symbiosis; triacylglycerols; Triglycerides; Triglycerides - biosynthesis
• ISSN: 0027-8424; 1091-6490
• DOI: 10.1073/pnas.0407076101

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.