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Decreasing mitochondrial fission alleviates hepatic steatosis in a murine model of nonalcoholic fatty liver disease.

Authors
  • Galloway, Chad A1
  • Lee, Hakjoo2
  • Brookes, Paul S1
  • Yoon, Yisang3
  • 1 Department of Anesthesiology, University of Rochester School of Medicine and Dentistry, Rochester, New York;
  • 2 Department of Physiology, Medical College of Georgia, Georgia Regents University, Augusta, Georgia. , (Georgia)
  • 3 Department of Physiology, Medical College of Georgia, Georgia Regents University, Augusta, Georgia [email protected] , (Georgia)
Type
Published Article
Journal
AJP Gastrointestinal and Liver Physiology
Publisher
American Physiological Society
Publication Date
Sep 15, 2014
Volume
307
Issue
6
Identifiers
DOI: 10.1152/ajpgi.00182.2014
PMID: 25080922
Source
Medline
Keywords
License
Unknown

Abstract

Mitochondria produce the majority of cellular ATP through oxidative phosphorylation, and their capacity to do so is influenced by many factors. Mitochondrial morphology is recently suggested as an important contributor in controlling mitochondrial bioenergetics. Mitochondria divide and fuse continuously, which is affected by environmental factors, including metabolic alterations. Underscoring its bioenergetic influence, altered mitochondrial morphology is reported in tissues of patients and in animal models of metabolic dysfunction. In this study, we found that mitochondrial fission plays a vital role in the progression of nonalcoholic fatty liver disease (NAFLD). The development of hepatic steatosis, oxidative/nitrative stress, and hepatic tissue damage, induced by a high-fat diet, were alleviated in genetically manipulated mice suppressing mitochondrial fission. The alleviation of steatosis was recapitulated in primary hepatocytes with the inhibition of mitochondrial fission. Mechanistically, our study indicates that fission inhibition enhances proton leak under conditions of free fatty acid incubation, implicating bioenergetic change through manipulating mitochondrial fission. Taken together, our results suggest a mechanistic role for mitochondrial fission in the etiology of NAFLD. The efficacy of decreasing mitochondrial fission in the suppression of NAFLD suggests that mitochondrial fission represents a novel target for therapeutic treatment of NAFLD.

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