William T Festuccia1. 1. Department of Physiology and Biophysics, Institute of Biomedical Sciences, University of Sao Paulo, Sao Paulo, 05508000, Brazil.
Abstract
SCOPE: Evidence gathered in the last decades suggests that lipotoxicity and inflammation are the main factors connecting adipose tissue dysfunction to the development of metabolic diseases such as insulin resistance, nonalcoholic fatty liver disease (NAFLD), cardiovascular disease, and certain types of cancer, among others. The mechanistic target of rapamycin (mTOR) is a serine threonine kinase that functions as the catalytic entity of two multiprotein complexes, mTOR complex 1 (mTORC1) and mTOR complex 2 (mTORC2). These complexes are important components of signaling pathways activated by nutrients, growth factors, and inflammatory mediators and are therefore directly involved in the regulation of adipocyte and macrophage metabolism and function. METHODS AND RESULTS: In this article, studies that evaluate the involvement of mTORC1 and 2 in the regulation of macrophage and adipocyte function and their implication in the development of metabolic-disease-associated adipose tissue dysfunction are reviewed. CONCLUSION: In adipocytes, optimal levels of mTORC1 activity are required for its pro-lipogenic actions, while in macrophages, mTORC1 regulates features of both M1 and M2 polarization. mTORC2, on the other hand, promotes glucose uptake and de novo lipogenesis in adipocytes and counteracts macrophage inflammatory response.
SCOPE: Evidence gathered in the last decades suggests that lipotoxicity and inflammation are the main factors connecting adipose tissue dysfunction to the development of metabolic diseases such as insulin resistance, nonalcoholic fatty liver disease (NAFLD), cardiovascular disease, and certain types of cancer, among others. The mechanistic target of rapamycin (mTOR) is a serine threonine kinase that functions as the catalytic entity of two multiprotein complexes, mTOR complex 1 (mTORC1) and mTOR complex 2 (mTORC2). These complexes are important components of signaling pathways activated by nutrients, growth factors, and inflammatory mediators and are therefore directly involved in the regulation of adipocyte and macrophage metabolism and function. METHODS AND RESULTS: In this article, studies that evaluate the involvement of mTORC1 and 2 in the regulation of macrophage and adipocyte function and their implication in the development of metabolic-disease-associated adipose tissue dysfunction are reviewed. CONCLUSION: In adipocytes, optimal levels of mTORC1 activity are required for its pro-lipogenic actions, while in macrophages, mTORC1 regulates features of both M1 and M2 polarization. mTORC2, on the other hand, promotes glucose uptake and de novo lipogenesis in adipocytes and counteracts macrophage inflammatory response.
Authors: Maynara L Andrade; Gustavo R Gilio; Luiz A Perandini; Albert S Peixoto; Mayara F Moreno; Érique Castro; Tiago E Oliveira; Thayna S Vieira; Milene Ortiz-Silva; Caroline A Thomazelli; Adriano B Chaves-Filho; Thiago Belchior; Patricia Chimin; Juliana Magdalon; Rachael Ivison; Deepti Pant; Linus Tsai; Marcos Y Yoshinaga; Sayuri Miyamoto; William T Festuccia Journal: Biochim Biophys Acta Mol Cell Biol Lipids Date: 2021-05-15 Impact factor: 5.228
Authors: Ashok Narasimhan; Xiaoling Zhong; Ernie P Au; Eugene P Ceppa; Atilla Nakeeb; Michael G House; Nicholas J Zyromski; C Max Schmidt; Katheryn N H Schloss; Daniel E I Schloss; Yunlong Liu; Guanglong Jiang; Bradley A Hancock; Milan Radovich; Joshua K Kays; Safi Shahda; Marion E Couch; Leonidas G Koniaris; Teresa A Zimmers Journal: Cancers (Basel) Date: 2021-04-20 Impact factor: 6.639