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

Emily J. Onufer, Shirli Tay, Lauren K. Barron, Cathleen M. Courtney, Brad W. Warner, Jun Guo

Research output: Contribution to journalArticle

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 that loss of intestinal specific-mTORC1 is protective of the development of diet-induced obesity by reducing food intake without altering the metabolic profile.

Original languageEnglish
Pages (from-to)1174-1179
Number of pages6
JournalBiochemical and Biophysical Research Communications
Volume505
Issue number4
DOIs
StatePublished - Nov 10 2018

Keywords

  • GDF-15
  • Obesity
  • Raptor
  • Small intestine
  • mTOR

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