Gestational exercise protects adult male offspring from high-fat diet-induced hepatic steatosis

Abstract

Background & aims: Mounting evidence indicates that maternal exercise confers protection to adult offspring against various diseases. Here we hypothesized that maternal exercise during gestation would reduce high-fat diet (HFD)-induced hepatic steatosis in adult rat offspring.

Methods: Following conception, pregnant dams were divided into either voluntary wheel running exercise (GE) or wheel-locked sedentary (GS) groups throughout gestation (days 4-21). Post-weaning, offspring received either normal chow diet (CD; 10% fat, 70% carbohydrate, 20% protein) or HFD (45% fat, 35% carbohydrate, and 20% protein) until sacrificed at 4- or 8-months of age.

Results: GE did not affect offspring birth weight or litter size. HFD feeding in offspring increased weight gain, body fat percentage, and glucose tolerance test area under the curve (GTT-AUC). Male offspring from GE dams had reduced body fat percentage across all ages (p<0.05). In addition, 8-month male offspring from GE dams were protected against HFD-induced hepatic steatosis, which was associated with increased markers of hepatic mitochondrial biogenesis (PGC-1α and TFAM), autophagic potential (ATG12:ATG5 conjugation) and hepatic triacylglycerol secretion (MTTP).

Conclusions: The current study provides the first evidence that gestational exercise can reduce susceptibility to HFD-induced hepatic steatosis in adult male offspring.

Keywords: Fetal origins; NAFLD; Rat.

Figure 1

Effects of age, GE, and HFD on offspring (A) bodyweight, (B) body fat percentage, (C) glucose tolerance in 8-mo offspring, and (D) voluntary physical activity. *, main effect of diet. ϕ, main effect of age. #, main effect of gestational condition. &, 2-mo activity greater than other ages. $, female activity greater than male activity.

Figure 2

Effects of age, GE, and HFD on offspring (A) liver TAG accumulation (B) histological hepatic steatosis in 8-mo male offspring. *, significant main effect of HFD. ϕ, main effect of age. Ω, 8-mo GS-HFD offspring greater than other groups by post-hoc pairwise comparison following significant 3-way interaction (age X diet X condition).

Figure 3

Effects of age, GE, and HFD on offspring (A) 1-[¹⁴C] palmitate oxidation, (B) β-HAD activity, and (C) citrate synthase activity in whole liver homogenate. ϕ, main effect of age.

Figure 4

Effects of GE and HFD on markers of mitochondrial biogenesis and autophagy in 8-mo male offspring. (A) PGC-1α mRNA, (B) TFAM mRNA, (C) ATG12:5 conjugation, (D) T172 p-AMPK/AMPK, (E) PPARγ protein. Representative western blots are presented above each respective graph. *, main effect of diet. #, main effect of gestational condition.

Figure 5

Effects of GE and HFD on markers of processes mediating hepatic triglyceride balance in 8-mo male offspring. (A) MTTP, (B) CD36, (D) S73 pACC/ACC, (E) ACC, and (F) FAS. Representative western blots are presented above each respective graph. *, significant main effect of HFD. #, significant main effect of GE.