Journal
CELLULAR AND MOLECULAR GASTROENTEROLOGY AND HEPATOLOGY
Volume 7, Issue 2, Pages 275-284Publisher
ELSEVIER INC
DOI: 10.1016/j.jcmgh.2018.09.017
Keywords
Nonalcoholic Steatohepatitis; Mitochondria; Pyruvate; Thiazolidinedione
Categories
Funding
- NIH [K99 HL136658, P30 DK052574, R01 DK104735]
Ask authors/readers for more resources
This article reviews the recent studies suggesting a potential role for inhibiting mitochondrial pyruvate metabolism as a strategy for treatment of nonalcoholic steatohepatitis. A hepatic comorbidity of metabolic syndrome, known as nonalcoholic fatty liver disease (NAFLD), is increasing in prevalence in conjunction with the pandemics of obesity and diabetes. The spectrum of NAFLD ranges from simple hepatic fat accumulation to a more severe disease termed nonalcoholic steatohepatitis (NASH), involving inflammation, hepatocyte death, and fibrosis. Importantly, NASH is linked to a much higher risk of cirrhosis, liver failure, and hepatocellular carcinoma, as well as an increased risk for nonhepatic malignancies and cardiovascular disease. Interest in the understanding of the disease processes and search for treatments for the spectrum of NAFLD-NASH has increased exponentially, but there are no approved pharmacologic therapies. In this review, we discuss the existing literature supporting insulin-sensitizing thiazolidinedione compounds as potential drug candidates for the treatment of NASH. In addition, we put these results into new context by summarizing recent studies suggesting these compounds alter mitochondrial metabolism by binding and inhibiting the mitochondrial pyruvate carrier.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available