Fredrik Bäckhed1, Hao Ding1,2, Ting Wang1, Lora V. Hooper1,3, Gou Young Koh1, András Nagy1, Clay F. Semenkovich1, Jeffrey I. Gordon1
1Center for Genome Sciences and Departments of Molecular Biology and Pharmacology, Genetics, and Medicine, Cell Biology, and Physiology, Washington University School of Medicine, St. Louis, MO 63110; Samuel Luenfeld Research Institute, Mount Sinai Hospital, Toronto, ON, Canada M5G 1X5; Biomedical Center, Department of Biological Sciences, Korea Advanced Institute of Science and Technology, Daejeon, 305-701, Republic of Korea; and Department of Medical Genetics and Microbiology, University of Toronto,...
2University of Manitoba
3Immunology
Tóm tắt
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.
