Insulin Resistance Linked to Reduced Mitochondrial Function
In fasting subjects, elevated free fatty acids and intramuscular fat accumulation could be cause
FRIDAY, Sept. 17 (HealthDay News) -- Insulin resistance appears to have a negative effect on mitochondrial function that isn't due to hyperglycemia, as seen in research on fasting individuals published in the September issue of Diabetes.
Joris Hoeks, Ph.D., of the Maastricht University Medical Centre in the Netherlands, and colleagues analyzed data from 12 healthy males (average age, 23.6 years) who underwent a 60-hour fast and a 60-hour period with normal feeding while in a respiration chamber. Afterward, the subjects underwent a hyperinsulinemic-euglycemic clamp and muscle biopsy.
The researchers found that levels of free fatty acid were increased roughly nine-fold after fasting, which led to higher lipid levels in the muscles and lower muscular insulin sensitivity. Although whole-body fat oxidation was increased, coupled state 3 respiration and maximally uncoupled respiration in muscle fibers were reduced. This latter finding wasn't explainable by changes in mitochondrial density, the authors write.
"Since prolonged fasting is a physiologic condition in which increased fat oxidation becomes very important, a reduced mitochondrial function seems unbeneficial from a physiologic point of view. Our findings suggest that the elevated plasma free fatty acid and/or intramuscular lipid levels associated with the insulin-resistant state are responsible for the secondary negative effects on mitochondrial function," the authors conclude.