Four weeks of exercise early in life reprograms adult skeletal muscle insulin resistance caused by a paternal high-fat diet

J Physiol. 2019 Jan;597(1):121-136. doi: 10.1113/JP276386. Epub 2018 Nov 22.

Abstract

Key points: A paternal high-fat diet/obesity before mating can negatively influence the metabolism of offspring. Exercise only early in life has a remarkable effect with respect to reprogramming adult rat offspring exposed to detrimental insults before conception. Exercise only early in life normalized adult whole body and muscle insulin resistance as a result of having a high-fat fed/obese father. Unlike the effects on the muscle, early exercise did not normalize the reduced adult pancreatic beta cell mass as a result of having a high-fat fed/obese father. Early-life exercise training may be able to reprogram an individual whose father was obese, inducing long-lasting beneficial effects on health.

Abstract: A paternal high-fat diet (HFD) impairs female rat offspring glucose tolerance, pancreatic morphology and insulin secretion. We examined whether only 4 weeks of exercise early in life could reprogram these negative effects. Male Sprague-Dawley rats consumed a HFD for 10 weeks before mating with chow-fed dams. Female offspring remained sedentary or performed moderate intensity treadmill exercise (5 days week-1 , 60 min day-1 , 20 m min-1 ) from 5 to 9 weeks of age. Paternal HFD impaired (P < 0.05) adult offspring whole body insulin sensitivity (i.p. insulin sensitivity test), as well as skeletal muscle ex vivo insulin sensitivity and TBC1D4 phosphorylation. It also lowered β-cell mass and reduced in vivo insulin secretion in response to an i.p. glucose tolerance test. Early-life exercise in offspring reprogrammed the negative effects of a paternal HFD on whole body insulin sensitivity, skeletal muscle ex vivo insulin-stimulated glucose uptake and TBC1D4 phosphorylation and also increased glucose transporter 4 protein. However, early exercise did not normalize the reduced pancreatic β-cell mass or insulin secretion. In conclusion, only 4 weeks of exercise early in life in female rat offspring reprograms reductions in insulin sensitivity in adulthood caused by a paternal HFD without affecting pancreatic β-cell mass or insulin secretion.

Keywords: Exercise; Fetal Programming; High fat diet; Insulin release; Mitochondria; Pancreas; Skeletal muscle.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Diet, High-Fat*
  • Fathers*
  • Female
  • GTPase-Activating Proteins / metabolism
  • Glucose Tolerance Test
  • Glucose Transporter Type 4 / metabolism
  • Insulin Resistance*
  • Male
  • Muscle, Skeletal / physiology*
  • Obesity
  • Pancreas / pathology
  • Physical Conditioning, Animal*
  • Rats, Sprague-Dawley

Substances

  • GTPase-Activating Proteins
  • Glucose Transporter Type 4
  • LOC686547 protein, rat
  • Slc2a4 protein, rat