Affiliation:
1. Laboratory of Morphometry, Metabolism, and Cardiovascular Diseases, Biomedical Centre, Institute of Biology Rio de Janeiro State University Rio de Janeiro Brazil
Abstract
AbstractObesity is related to several organs, but the liver is particularly affected. Adenosine monophosphate‐activated protein kinase (AMPK) is a cellular energy sensor and regulator of liver lipid dysfunction and glucose metabolism. The mechanistic target of rapamycin (mTOR) is a protein kinase regulating cell growth, survival, metabolism, and immunity. Together, these pathways are involved in obesity, insulin resistance, non‐alcoholic fatty liver disease (NAFLD) and its progression, and autophagy. During energy demand, liver kinase B (LKB) phosphorylation helps activate the AMPK/mTOR pathways. Likewise, the protein forkhead box O family (FOXO) negatively regulates adipogenesis by binding to the promoter sites of peroxisome proliferator‐activated receptor‐gamma coactivator 1‐alpha, initiating adipogenesis. In addition, acetyl‐CoA carboxylase, which regulates de novo lipogenesis, is linked to LKB and FOXO in developing NAFLD. The kinase complex, consisting of Unc‐51‐like autophagy‐activating kinase 1 or 2 (ULK1, ULK2) by stimulating autophagy, and eliminating fat droplets in NAFLD, is regulated by mTORC1 and negatively regulated by AMPK that suppresses liver lipogenesis and increases fatty acid oxidation. Also, ULK1 is essential for initiating phagophore formation, establishing macrophagy, and generating autophagosomes. The selective breakdown of lipid droplets through macroautophagy, or macrolipophagy, occurs on a cellular energy level using free fatty acids. In addition, mTORC1 promotes lipogenesis by activating sterol regulatory element‐binding protein. Finding new components and novel regulatory modes in signaling is significant for a better understanding of the AMPK/mTOR pathways, potentially facilitating the development of future diagnostic and therapeutic strategies for NAFLD and its progression to non‐alcoholic steatohepatitis, cirrhosis, and hepatocellular carcinoma.
Funder
Fundação Carlos Chagas Filho de Amparo à Pesquisa do Estado do Rio de Janeiro
Conselho Nacional de Desenvolvimento Científico e Tecnológico
Coordenação de Aperfeiçoamento de Pessoal de Nível Superior
Subject
Gastroenterology,Hepatology
Cited by
4 articles.
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