Constitutive Activation of the Nutrient Sensor mTORC1 in Myeloid Cells Induced by Tsc1 Deletion Protects Mice from Diet-Induced Obesity

Molecular Nutrition & Food Research
Vivian A PaschoalWilliam T Festuccia

Abstract

To test whether myeloid cells Tsc1 deletion and therefore constitutive activation of the nutrient sensor mTORC1 protects from high-fat diet (HFD)-induced obesity, glucose intolerance, and adipose tissue inflammation. Mice with Tsc1 deletion in myeloid cells (MTsc1KO) and littermate controls (MTsc1WT) were fed with HFD for 8 weeks and evaluated for body weight, glucose homeostasis, and adipose tissue inflammation. MTsc1KO mice were protected from HFD-induced obesity and glucose intolerance. MTsc1KO, however, displayed, independently of the diet, abnormal behavior, episodes of intense movement, and muscle spasms followed by temporary paralysis. To investigate whether obesity protection was due to myeloid cells Tsc1 deletion, bone marrow was transplanted from MTsc1WT and MTsc1KO into irradiated C57BL6/J mice. Mice transplanted with MTsc1KO bone marrow displayed reduced body weight gain, adiposity, and inflammation, and enhanced energy expenditure, glucose tolerance and adipose tissue M2 macrophage content upon HFD feeding, in the absence of abnormal behavior. In vitro, Tsc1 deletion increased in a mTORC1-dependent manner macrophage polarization to M2 profile and mRNA levels of fatty acid binding protein 4 and PPARγ. Constitutive m...Continue Reading

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Citations

Jan 9, 2019·Journal of Molecular Endocrinology·Ayse Basak EnginIpek Isik Gonul
Feb 28, 2020·Molecular Nutrition & Food Research·William T Festuccia

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