The effects of acute BPA exposure on skeletal muscle mitochondrial function and glucose metabolism

Mol Cell Endocrinol. 2020 Jan 1;499:110580. doi: 10.1016/j.mce.2019.110580. Epub 2019 Sep 16.


Bisphenol A (BPA) is an environmental pollutant that has been associated with adverse health effects including skeletal muscle insulin resistance, a major contributor to the pathogenesis of type 2 diabetes (T2D). Early mitochondrial dysfunction and oxidative stress are linked to impaired glucose metabolism in skeletal muscle. In this study, we investigated the effects of BPA on skeletal muscle mitochondrial function and insulin sensitivity. L6 myotubes were treated with BPA (1 nM-105 nM) during the last 24 h of differentiation. Following exposure to 105 nM of BPA, resting and maximal oxygen consumption rates were decreased, whereas mitochondrial proton leak was increased. Overall metabolic activity, measured by redox ability, was decreased in L6 myotubes exposed to 105 nM of BPA. At this concentration, insulin-stimulated glucose uptake was increased, which corresponded to an increased phosphorylation of the insulin signaling protein Akt, and increased glycolysis measured by extracellular acidification rate (ECAR). Acute BPA exposure did not alter levels of oxidative stress markers in muscle cells, but significantly increased mitochondrial proton leak, which is known to be involved in decreased ROS production. The effects of BPA on glucose uptake, but not mitochondrial function, were reversed by the use of an estrogen receptor antagonist. These results suggest that acute exposure of L6 myotubes at only high concentrations of BPA alters glucose metabolism, which is likely a compensatory response to reduced mitochondrial energy production capacity.

Keywords: Bisphenols; Glucose metabolism; Insulin signaling; Oxidative phosphorylation; Oxidative stress; Skeletal muscle.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Benzhydryl Compounds / adverse effects*
  • Cell Line
  • Cell Survival / drug effects
  • Glucose / metabolism*
  • Glycolysis / drug effects
  • Insulin Resistance
  • Mitochondria / drug effects
  • Mitochondria / metabolism*
  • Muscle Fibers, Skeletal / cytology*
  • Muscle Fibers, Skeletal / drug effects
  • Muscle Fibers, Skeletal / metabolism
  • Oxygen Consumption / drug effects
  • Phenols / adverse effects*
  • Phosphorylation / drug effects
  • Proto-Oncogene Proteins c-akt / metabolism
  • Rats


  • Benzhydryl Compounds
  • Phenols
  • Proto-Oncogene Proteins c-akt
  • Glucose
  • bisphenol A