The gut microbiota as an environmental factor that regulates fat storage

Fredrik Bäckhed, Hao Ding, Ting Wang, Lora V. Hooper, Young Koh Gou, Andras Nagy, Clay F. Semenkovich, Jeffrey I. Gordon

Research output: Contribution to journalArticleResearchpeer-review

3272 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)15718-15723
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume101
Issue number44
DOIs
Publication statusPublished - 2 Nov 2004
Externally publishedYes

Keywords

  • Adiposity
  • Energy storage
  • Fasting-induced adipose factor
  • Nutrient processing
  • Symbiosis

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