Mitochondria are the nexus of energy metabolism and consequently their dysfunction has been implicated in the development of metabolic complications and the progression to insulin resistance and type II diabetes. The unique tetra-acyl phospholipid cardiolipin (CL) is located in the inner mitochondrial membrane where it maintains mitochondrial integrity. Here we show that knock-down of Tafazzin (TAZ kd), a CL transacylase, in mice results in protection against the development of obesity, insulin resistance and hepatic steatosis. We determined that hypermetabolism protected TAZ kd mice from weight gain. Unexpectedly, the large reduction of CL in the heart and skeletal muscle of TAZ kd mice was not mirrored in the liver. As a result, TAZ kd mice exhibited normal hepatic mitochondrial supercomplex formation and elevated hepatic fatty acid oxidation. Collectively, these studies identify a key role for hepatic CL remodelling in regulating susceptibility to insulin resistance and as a novel therapeutic target for diet-induced obesity.
- Received January 22, 2016.
- Accepted July 26, 2016.
- © 2016 by the American Diabetes Association.