Intestinal epithelial cell-specific Raptor is essential for high fat diet-induced weight gain in mice
In: Biochemical and Biophysical Research Communications, Jg. 505 (2018-11-01), S. 1174-1179
Online
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Zugriff:
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.
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Intestinal epithelial cell-specific Raptor is essential for high fat diet-induced weight gain in mice
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Autor/in / Beteiligte Person: | Barron, Lauren ; Tay, Shirli ; Guo, Jun ; Warner, Brad W. ; Courtney, Cathleen M. ; Onufer, Emily J. |
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Zeitschrift: | Biochemical and Biophysical Research Communications, Jg. 505 (2018-11-01), S. 1174-1179 |
Veröffentlichung: | Elsevier BV, 2018 |
Medientyp: | unknown |
ISSN: | 0006-291X (print) |
DOI: | 10.1016/j.bbrc.2018.10.040 |
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