Intestinal epithelial cell-specific Raptor is essential for high fat diet-induced weight gain in mice.

Intestinal epithelial cell-specific Raptor is essential for high fat diet-induced weight gain in mice. Biochem Biophys Res Commun. 2018 Oct 12;: Authors: Onufer EJ, Tay S, Barron LK, Courtney CM, Warner BW, Guo J Abstract Mammalian target of rapamycin complex 1 (mTORC1) is a major regulator of cell growth and proliferation through fuel sensing. Systemic inhibition of mTOR as well as manipulation of its downstream products prevent diet-induced obesity. The purpose of this study was to determine the consequences of intestine-targeted mTORC1 inhibition. To attenuate intestinal mTORC1 activity, Villin-CreER mice were crossed with Raptorflox/flox mice, creating an intestinal-specific Raptor null line (i-Raptor -/-). Mice were fed a high fat diet (HFD) and compositional changes as well as food intake levels were assessed. Over a five-week time course, i-Raptor -/- mice consistently gained less body weight on a HFD compared to wildtype (WT) mice secondary to significantly reduced food intake. Importantly, the i-Raptor -/- mice did not appear to be malnourished, demonstrated by their preservation of lean body mass. i-Raptor -/- mice also maintained a normal metabolic profile without significant changes in triglyceride or fasting glucose levels. Further investigation revealed that GDF-15 mRNA expression was significantly enhanced in i-Raptor -/- enterocytes when refed with HFD after overnight starvation. In summary, our study establishes...
Source: Biochemical and Biophysical Research communications - Category: Biochemistry Authors: Tags: Biochem Biophys Res Commun Source Type: research