Effect Of Exercise On Skeletal Muscle Lipogenic Gene Expression During Weight Regain
Authors: Presby David , Houck Julie , Giles Erin , Steig Amy , Jackman Matthew R. , Foright Rebecca , Johnson Ginger C , Higgins Janine , MacLean Paul S 
Published: November 2023

Background

Exercise has been shown in pre‐clinical models to attenuate weight regain by reducing food intake and increasing energy expenditure beyond the cost of the exercise bout. We have shown that this energy gap is due, at least in part, to an increase in the trafficking of excess nutrients through the energetically expensive pathway of de novo lipogenesis. Diverting nutrients through this pathway prior to oxidation could serve to dissipate excess energy during weight regain. The purpose of the present study was to determine if regular exercise increases skeletal muscle lipogenic gene expression during weight regain.

Methods

Male Wistar Rats were selected for their propensity to become obese when challenged with a high fat diet (HFD). These rats were then maintained on a low fat diet (LFD) for a period of 16 weeks. An obese control (OB) was maintained on an ad libitum LFD through the duration of the study. The rest of the animals were calorically restricted for two weeks, which led to a 14–18% loss in body weight, and then maintained this weight for 6 weeks. Once in the weight maintenance phase half of the animals were intervened with an exercise condition (EX), while the other half sustained sedentary conditions (SED). Exercising and sedentary animals were further split into two groups: (1) a group where restricted food access was maintained throughout the duration of the study; and (2) a group that had ad libitum access to food for the final 24 hours of the study. An additional sedentary group had their caloric excess matched with the exercise group (SED‐GM). 24 hours prior to sacrifice, intraperitoneal injections of tritiated H2O were used to assess the incorporation of the tritium label into de novo derived lipids of gastrocnemius. qRT‐PCR and western blotting were performed on the gastrocnemius muscle to quantify mRNA and proteins known to be involved in the process of de novo lipogenesis.

Results

Compared to REL‐GM, EX ad libitum animals retained more tritium within their gastrocnemius (P=0.035). Relative to SED ad libitum, EX ad libitum rats had decreased expression of DGAT1 (P=0.006), while the differences in DGAT2, FAS, GPAM, and SCD1 did not reach significance. Relative to SED‐GM, EX ad libitum rats displayed a decrease in DGAT2 (P=0.047) and FASN (P=0.035) expression, while DGAT1, GPAM, and SCD1 did not reach significance. Protein content of fatty acid synthase was reduced in EX ad libitum when compared to REL‐GM (P=0.04).

Conclusion

Contrary to our hypothesis, regular exercise did not increase the lipogenic capacity of skeletal muscle during weight gain after weight loss. Our observations would suggest that exercise may not leverage this pathway in skeletal muscle to dissipate excess energy during weight regain. Rather, we suspect that the enrichment of lipid pools with de novo derived lipids may be the result of diverting excess nutrients through hepatic, rather than muscle, de novo lipogenesis.

Support or Funding Information

NIH P50 HD073063, P30 DK 48520