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Impaired Cardiolipin Biosynthesis Prevents Hepatic Steatosis and Diet-Induced Obesity.


ABSTRACT: Mitochondria are the nexus of energy metabolism, and consequently their dysfunction has been implicated in the development of metabolic complications and progression to insulin resistance and type 2 diabetes. The unique tetra-acyl phospholipid cardiolipin (CL) is located in the inner mitochondrial membrane, where it maintains mitochondrial integrity. Here we show that knockdown 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 remodeling in regulating susceptibility to insulin resistance and as a novel therapeutic target for diet-induced obesity.

SUBMITTER: Cole LK 

PROVIDER: S-EPMC5079636 | biostudies-literature | 2016 Nov

REPOSITORIES: biostudies-literature

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Impaired Cardiolipin Biosynthesis Prevents Hepatic Steatosis and Diet-Induced Obesity.

Cole Laura K LK   Mejia Edgard M EM   Vandel Marilyne M   Sparagna Genevieve C GC   Claypool Steven M SM   Dyck-Chan Laura L   Klein Julianne J   Hatch Grant M GM  

Diabetes 20160805 11


Mitochondria are the nexus of energy metabolism, and consequently their dysfunction has been implicated in the development of metabolic complications and progression to insulin resistance and type 2 diabetes. The unique tetra-acyl phospholipid cardiolipin (CL) is located in the inner mitochondrial membrane, where it maintains mitochondrial integrity. Here we show that knockdown of Tafazzin (TAZ kd), a CL transacylase, in mice results in protection against the development of obesity, insulin resi  ...[more]

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