Impaired cardiolipin biosynthesis prevents hepatic steatosis and diet-induced obesity

Laura K. Cole, Edgard M. Mejia, Marilyne Vandel, Genevieve C. Sparagna, Steven M Claypool, Laura Dyck-Chan, Julianne Klein, Grant M. Hatch

Research output: Contribution to journalArticle

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.

Original languageEnglish (US)
Pages (from-to)3289-3300
Number of pages12
JournalDiabetes
Volume65
Issue number11
DOIs
StatePublished - Nov 1 2016

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Cardiolipins
Obesity
Diet
Liver
Insulin Resistance
Mitochondrial Membranes
Type 2 Diabetes Mellitus
Energy Metabolism
Weight Gain
Phospholipids
Myocardium
Mitochondria
Skeletal Muscle
Fatty Acids

ASJC Scopus subject areas

  • Internal Medicine
  • Endocrinology, Diabetes and Metabolism

Cite this

Cole, L. K., Mejia, E. M., Vandel, M., Sparagna, G. C., Claypool, S. M., Dyck-Chan, L., ... Hatch, G. M. (2016). Impaired cardiolipin biosynthesis prevents hepatic steatosis and diet-induced obesity. Diabetes, 65(11), 3289-3300. https://doi.org/10.2337/db16-0114

Impaired cardiolipin biosynthesis prevents hepatic steatosis and diet-induced obesity. / Cole, Laura K.; Mejia, Edgard M.; Vandel, Marilyne; Sparagna, Genevieve C.; Claypool, Steven M; Dyck-Chan, Laura; Klein, Julianne; Hatch, Grant M.

In: Diabetes, Vol. 65, No. 11, 01.11.2016, p. 3289-3300.

Research output: Contribution to journalArticle

Cole, LK, Mejia, EM, Vandel, M, Sparagna, GC, Claypool, SM, Dyck-Chan, L, Klein, J & Hatch, GM 2016, 'Impaired cardiolipin biosynthesis prevents hepatic steatosis and diet-induced obesity', Diabetes, vol. 65, no. 11, pp. 3289-3300. https://doi.org/10.2337/db16-0114
Cole LK, Mejia EM, Vandel M, Sparagna GC, Claypool SM, Dyck-Chan L et al. Impaired cardiolipin biosynthesis prevents hepatic steatosis and diet-induced obesity. Diabetes. 2016 Nov 1;65(11):3289-3300. https://doi.org/10.2337/db16-0114
Cole, Laura K. ; Mejia, Edgard M. ; Vandel, Marilyne ; Sparagna, Genevieve C. ; Claypool, Steven M ; Dyck-Chan, Laura ; Klein, Julianne ; Hatch, Grant M. / Impaired cardiolipin biosynthesis prevents hepatic steatosis and diet-induced obesity. In: Diabetes. 2016 ; Vol. 65, No. 11. pp. 3289-3300.
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