Transgenerational Effects of Physical Activity Ancestry on Mouse Body Composition, Glucose Metabolism, and Gene Expression

Abstract

PURPOSE: To examine the influence of a physical activity (PA) ancestry compared to a sedentary (SED) ancestry on body composition, glucose metabolism, and skeletal muscle gene expression in multiple generations of mouse offspring. METHODS: C57/Bl6 mice (F0) were exposed to PA (voluntary wheel running, N=20) or a SED condition (no wheel access, N=20) for 12 weeks prior to breeding. PA males were bred with PA females and SED males were bred with SED females to produce F1 pups. PA animals had continued access to the running wheel during breeding, pregnancy, and weaning. F1 pups were either sacrificed at 8 wk without exposure to PA (PA ancestry was the only distinguishing feature), or bred with F1 littermates to produce an F2 generation. Similarly, F2 offspring were sacrificed at 8 wk without any PA exposure. Body, muscle (quadriceps, gastrocnemius, plantaris, soleus, TA, EDL), and omental fat mass and glucose tolerance were measured in F1 and F2 offspring. mRNA expression of several metabolic genes (Ppargc1a, Pdk4, Ppara, Ppard, Alas1, Hk2, Cycs, Cs, and Mt-co1) was measured in gastrocnemius muscle of F1 and F2 offspring. RESULTS: Body (p<0.01) and omental fat (p<0.01) mass were lower in the F1 females with PA compared to SED ancestry. Average TA (p<0.01) and soleus (p=0.05) mass were lower in F1 females with a PA compared to SED ancestry. Average soleus (p=0.03) and quadriceps (p=0.04) mass were lower, while average EDL mass was greater (p=0.02) in F1 males with a PA compared to SED ancestry. No other body, fat, or muscle mass differences were observed. Glucose AUC was smaller (p=0.01) in PA F0 females compared to their SED counterparts. There were no differences in glucose AUC between ancestries in the F1 generation, but glucose AUC was smaller in F2 females with a SED compared to PA ancestry (p=0.01). No differences in mRNA level of Pdk4, Ppara, Alas1, or Cs were observed due to ancestry (PA vs. SED ancestry in the F1 or the F2 generation). mRNA levels were lower for Ppargc1a (p=0.03), Hk2 (p=0.03), Mt-co1(p=0.05), and Ppard (p<0.01) in F1 males with a PA compared to a SED ancestry. Cycs mRNA levels were greater (p=0.03) in F2 males with a PA compared to a SED ancestry. mRNA levels were higher for Ppargc1a (p=0.02) and tended to be higher for Ppard (p=0.06) in F2 females with a PA compared to a SED ancestry. CONCLUSIONS: These preliminary findings indicate that PA ancestry (independent of direct PA) can influence aspects of body composition, glucose metabolism, and skeletal muscle metabolic gene expression in multiple generations of mouse offspring. This work was supported by the School of Public Health Research Seed Money Program at UMD.