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Int. J. Mol. Sci. 2018, 19(7), 2034;

New Aspects of Lipotoxicity in Nonalcoholic Steatohepatitis

Liver Research Unit, Medica Sur Clinic & Foundation, 14050 Mexico City, Mexico
Department of General Internal Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA
Department of Gastroenterology, National Medical Center “20 Noviembre”, 03229 Mexico City, Mexico
Obesity Clinic, General Hospital “Dr. Manuel Gea González”, 14080 Mexico City, Mexico
Author to whom correspondence should be addressed.
Received: 6 June 2018 / Revised: 9 July 2018 / Accepted: 11 July 2018 / Published: 13 July 2018
(This article belongs to the Special Issue Hepatotoxicity: Molecular Mechanisms and Pathophysiology)
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NASH is becoming increasingly common worldwide because of the growing global prevalence of obesity and consequently NAFLD. Unfortunately, the mechanism of progression of NAFLD to NASH and then cirrhosis is not completely understood. Several factors, including insulin resistance, inflammation, oxidative stress, lipotoxicity, and bile acid (BA) toxicity, have been reported to be associated with NASH progression. The release of fatty acids from dysfunctional and insulin-resistant adipocytes results in lipotoxicity, which is caused by the ectopic accumulation of triglyceride-derived toxic metabolites and the subsequent activation of inflammatory pathways, cellular dysfunction, and lipoapoptosis. Adipose tissue (AT), especially visceral AT, comprises multiple cell populations that produce adipokines and insulin-like growth factor, plus macrophages and other immune cells that stimulate the development of lipotoxic liver disease. These biomolecules have been recently linked with many digestive diseases and gastrointestinal malignancies such as hepatocellular carcinoma. This made us question what role lipotoxicity has in the natural history of liver fibrosis. Therefore, this review focuses on the close relationship between AT and NASH. A good comprehension of the pathways that are related to dysregulated AT, metabolic dysfunction, and hepatic lipotoxicity will result in the development of prevention strategies and promising therapeutics for patients with NASH. View Full-Text
Keywords: nonalcoholic steatohepatitis; liver fibrosis; hepatic lipotoxicity nonalcoholic steatohepatitis; liver fibrosis; hepatic lipotoxicity

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This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited (CC BY 4.0).

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Mendez-Sanchez, N.; Cruz-Ramon, V.C.; Ramirez-Perez, O.L.; Hwang, J.P.; Barranco-Fragoso, B.; Cordova-Gallardo, J. New Aspects of Lipotoxicity in Nonalcoholic Steatohepatitis. Int. J. Mol. Sci. 2018, 19, 2034.

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