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Obes Rev. 2012 Dec;13 Suppl 2:40-50. doi: 10.1111/j.1467-789X.2012.01036.x.

Revisiting the diacylglycerol-induced insulin resistance hypothesis.

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Department of Physiology, University of Lausanne, 7 Bugnon, Lausanne, Switzerland.


Obesity is associated with skeletal muscle insulin resistance, which is a crucial step in the development of type 2 diabetes. Among the mechanisms by which obesity may lead to insulin resistance, lipotoxicity is one of the hypotheses being explored; others include inflammation or the oxidative stress hypotheses. This review focuses on the role of diacylglycerols (DAG), a family of lipid metabolites implicated in the pathogenesis of lipotoxicity and insulin resistance. While recent studies report contradictory results in humans with regard to the importance of DAG-induced insulin resistance in skeletal muscle, other current literature highlight a potential role for DAG as signalling molecules. This review will discuss possible hypotheses explaining these contradictory results and the need to explore further the role of DAG in human metabolism.

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