| First Author | Onufer EJ | Year | 2018 |
| Journal | Biochem Biophys Res Commun | Volume | 505 |
| Issue | 4 | Pages | 1174-1179 |
| PubMed ID | 30318117 | Mgi Jnum | J:270384 |
| Mgi Id | MGI:6276723 | Doi | 10.1016/j.bbrc.2018.10.040 |
| Citation | Onufer EJ, et al. (2018) Intestinal epithelial cell-specific Raptor is essential for high fat diet-induced weight gain in mice. Biochem Biophys Res Commun 505(4):1174-1179 |
| abstractText | 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-Cre(ER) mice were crossed with Raptor(flox/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 that loss of intestinal specific-mTORC1 is protective of the development of diet-induced obesity by reducing food intake without altering the metabolic profile. |
