Adipose tissue and liver adaptations in exercised versus non-exercised rats fed a ketogenic diet, western diet, or standard rodent chow

Abstract

BACKGROUND: We investigated the effects of a low-carbohydrate ketogenic diet (KD), versus other diets, on adipose tissue, liver and serum biomarkers in exercise-trained versus sedentary rodents. METHODS: Male Sprague-Dawley rats (~9-10 weeks of age) remained sedentary (SED) or exercised daily with resistance-loaded running wheels (EX) over 6 weeks. Rats were provided isocaloric amounts of KD (20.2% protein, 10.3% carbohydrate, 69.5% fat), Western diet (WD; 15.2% protein, 42.7 carbohydrate, 42.0% fat), or Standard Chow (SC; 24.0% protein, 58.0% carbohydrate, 18.0% fat); n=8-10 in each diet group for SED and EX rats. Upon euthanasia, body and select adipose tissue masses were recorded and preserved for analyses, and liver and serum were also removed and preserved for analyses. RESULTS: Body mass and feed efficiency was greater in WD- and SC-fed vs. KD-fed rats (p<0.001). Diet (WD>KD=SC, p<0.05) and activity (SED>EX, p<0.05) effects existed for raw and relative (body mass-adjusted) omental adipose tissue (OMAT) masses. OMAT adipocyte diameters were lowest in KD-fed rats (p<0.01). Activity effects (EX>SED, p<0.05 to p<0.001) existed for OMAT acetyl Co-A carboxylase (ACC), phospho/pan-p65 (Ser536), phospho/pan-AMPK (Thr172), phospho/pan-HSL (Ser563), and uncoupling protein-1 (UCP-1) protein expression patterns. Raw inguinal/subcutaneous (SQ) masses were greater in WD vs. KD-fed rats (p<0.01), and diet (WD>KD, p<0.05) and activity (SED>EX, p<0.01) effects existed for raw subscapular brown adipose tissue (BAT) masses. Diet effects existed for liver triglycerides (WD>KD=SC, p<0.001), and diet (WD=SC>KD, p<0.05) and activity effects (SED>EX, p=0.01) existed for liver phospho/pan-p65. Diet (WD=SC>KD, p<0.001) and activity (SED>EX, p<0.001) effects existed for serum insulin, and diet (KD>SC, p<0.01) and activity (SED>EX, p<0.01) effects existed for serum β-hydroxybutyrate (BHB). In all rats, serum insulin was positively associated with body mass (r=0.54, p<0.001), feed efficiency (r=0.57, p<0.001), relative OMAT mass (r=0.57, p<0.001), and relative SQ mass (r=0.31, p<0.05). CONCLUSIONS: While KD-fed rats weighed less and had lower adipose tissue masses compared to WD- and/or SC-fed rats, exercise did not enhance body or fat mass maintenance and/or further alter adipose tissue, liver or serum biomarkers in KD-fed rats. Notwithstanding, the association data suggest lower insulin with KD and/or exercise may facilitate attenuation of adipose tissue mass accretion in rodents.