Effects of a ketogenic diet on adipose tissue, liver, and serum biomarkers in sedentary rats and rats that exercised via resisted voluntary wheel running

Angelia Maleah Holland, Wesley C. Kephart, Petey W. Mumford, Christopher Brooks Mobley, Ryan P. Lowery, Joshua J. Shake, Romil K. Patel, James C. Healy, Danielle J. McCullough, Heidi A. Kluess, Kevin W. Huggins, Andreas N. Kavazis, Jacob M. Wilson, Michael D. Roberts

Research output: Contribution to journalArticle

21 Scopus citations


We investigated the effects of different diets on adipose tissue, liver, serum morphology, and biomarkers in rats that voluntarily exercised. Male Sprague-Dawley rats (~9–10 wk of age) exercised with resistanceloaded voluntary running wheels (EX; wheels loaded with 20–60% body mass) or remained sedentary (SED) over 6 wk. EX and SED rats were provided isocaloric amounts of either a ketogenic diet (KD; 20.2%-10.3%-69.5% protein-carbohydrate-fat), a Western diet (WD; 15.2%-42.7–42.0%), or standard chow (SC; 24.0%-58.0%-18.0%); n =8–10 in each diet for SED and EX rats. Following the intervention, body mass and feed efficiency were lowest in KD rats, independent of exercise (P < 0.05). Absolute and relative (body massadjusted) omental adipose tissue (OMAT) masses were greatest in WD rats (P < 0.05), and OMAT adipocyte diameters were lowest in KD-fed rats (P < 0.05). None of the assayed OMAT or subcutaneous (SQ) protein markers were affected by the diets[total acetyl coA carboxylase (ACC), CD36, and CEBPα or phosphorylated NF-κB/ p65, AMPKα, and hormone-sensitive lipase (HSL)], although EX unexpectedly altered some OMAT markers (i.e., higher ACC and phosphorylated NF-κB/p65, and lower phosphorylated AMPKα and phosphorylated HSL). Liver triglycerides were greatest in WD rats (P < 0.05), and liver phosphorylated NF-κB/p65 was lowest in KD rats (P < 0.05). Serum insulin, glucose, triglycerides, and total cholesterol were greater in WD and/or SC rats compared with KD rats (P < 0.05), and serum β-hydroxybutyrate was greater in KD vs. SC rats (P < 0.05). In conclusion, KD rats presented a healthier metabolic profile, albeit the employed exercise protocol minimally impacts any potentiating effects that KD has on fat loss.

Original languageEnglish (US)
Pages (from-to)R337-R351
JournalAmerican Journal of Physiology - Regulatory Integrative and Comparative Physiology
Issue number2
Publication statusPublished - Aug 2016



  • Adipose tissue
  • Exercise
  • Insulin
  • Ketogenic diet
  • Liver

ASJC Scopus subject areas

  • Physiology
  • Physiology (medical)

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