Mitochondrial ATP transporter depletion protects mice against liver steatosis and insulin resistance
© 2017 The Author(s). Non-alcoholic fatty liver disease (NAFLD) is a common metabolic disorder in obese individuals. Adenine nucleotide translocase (ANT) exchanges ADP/ATP through the mitochondrial inner membrane, and Ant2 is the predominant isoform expressed in the liver. Here we demonstrate that targeted disruption of Ant2 in mouse liver enhances uncoupled respiration without damaging mitochondrial integrity and liver functions. Interestingly, liver specific Ant2 knockout mice are leaner and resistant to hepatic steatosis, obesity and insulin resistance under a lipogenic diet. Protection against fatty liver is partially recapitulated by the systemic administration of low-dose carboxyatractyloside, a specific inhibitor of ANT. Targeted manipulation of hepatic mitochondrial metabolism, particularly through inhibition of ANT, may represent an alternative approach in NAFLD and obesity treatment.
Digital Object Identifier (DOI)
Cho, Joonseok; Zhang, Yujian; Park, Shi Young; Joseph, Anna Maria; Han, Chul; Park, Hyo Jin; Kalavalapalli, Srilaxmi; Chun, Sung Kook; Morgan, Drake; Kim, Jae Sung; Someya, Shinichi; Mathews, Clayton E.; Lee, Young Jae; Wohlgemuth, Stephanie E.; Sunny, Nishanth E.; Lee, Hui Young; Choi, Cheol Soo; Shiratsuchi, Takayuki; Oh, S. Paul; and Terada, Naohiro, "Mitochondrial ATP transporter depletion protects mice against liver steatosis and insulin resistance" (2017). Translational Neuroscience. 653.