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.
