Mitochondrial ATP transporter depletion protects mice against liver steatosis and insulin resistance.
basic_science · Level V
Where this comes from
- Record sourced from PubMed, PMID 28205519.
- Also identified by DOI 10.1038/ncomms14477 and PMC identifier 5316896.
- Licence recorded as CC BY.
- The licence permits redistribution, so the abstract is shown in full and the full text is available from the publisher.
Abstract
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.
Medical subject headings
- Adenine Nucleotide Translocator 2
- Adenosine Triphosphate
- Fatty Liver
- Insulin Resistance
- Mitochondria, Liver
- Protective Agents