Early Skeletal Muscle Adaptations to Short-Term High-Fat Diet in Humans Before Changes in Insulin Sensitivity

Obesity (Silver Spring). 2015 Apr;23(4):720-4. doi: 10.1002/oby.21031.

Abstract

Objective: The purpose of this investigation was to understand the metabolic adaptations to a short-term (5 days), isocaloric, high-fat diet (HFD) in healthy, young males.

Methods: Two studies were undertaken with 12 subjects. Study 1 investigated the effect of the HFD on skeletal muscle substrate metabolism and insulin sensitivity. Study 2 assessed the metabolic and transcriptional responses in skeletal muscle to the transition from a fasted to fed state using a high-fat meal challenge before and after 5 days of the HFD.

Results: Study 1 showed no effect of a HFD on skeletal muscle metabolism or insulin sensitivity in fasting samples. Study 2 showed that a HFD elicits significant increases in fasting serum endotoxin and disrupts the normal postprandial excursions of serum endotoxin, as well as metabolic and transcriptional responses in skeletal muscle. These effects after 5 days of the HFD were accompanied by an altered fasting and postprandial response in the ratio of phosphorylated- to total-p38 protein. These changes all occurred in the absence of alterations in insulin sensitivity.

Conclusions: Our findings provide evidence for early biological adaptations to high-fat feeding that proceed and possibly lead to insulin resistance.

Publication types

  • Comparative Study
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adaptation, Physiological
  • Adult
  • Diet, High-Fat*
  • Dietary Fats / administration & dosage*
  • Humans
  • Insulin Resistance / physiology*
  • Male
  • Muscle Fibers, Skeletal / metabolism
  • Muscle, Skeletal / metabolism*
  • Postprandial Period
  • Young Adult

Substances

  • Dietary Fats