Improved Mitochondrial Function Is Linked With Improved Insulin Sensitivity Through Reductions in FFA

  1. Paul M. Coen
  1. Translational Research Institute for Metabolism and Diabetes, Florida Hospital, Sanford-Burnham Medical Research Institute, Orlando, FL
  1. Corresponding author: Bret H. Goodpaster, bret.goodpaster{at}flhosp.org.

Skeletal muscle insulin resistance (IR) is inextricably linked with the etiology of type 2 diabetes (T2D) and is a key target for prevention and treatment strategies. IR likely has many mechanistic origins, but the primary causes remain elusive, particularly in humans. Of the many possible mediators of IR, a considerable body of work has debated the potential roles of mitochondria (13), lipid oversupply (i.e., “lipotoxicity”) (4,5), and the association between mitochondria, fatty acid metabolism, and intramyocellular lipid accumulation—the subject of this article. Indeed, substantial evidence exists to both support and refute a role for mitochondria in skeletal muscle insulin resistance (6,7).

In this issue, Daniele et al. (8) examined the associations among chronic free fatty acid (FFA) levels, intramyocellular lipids, the capacity for skeletal muscle mitochondrial ATP production and IR in human obesity and T2D. These investigators used a 2-week, single-arm, open-label acipimox treatment, which, consistent with this group’s previous studies (9,10), significantly reduced circulating FFA levels and presumably availability to muscle and improved insulin sensitivity. The authors’ central hypothesis was that chronic …

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