Treating NAFLD in OLETF rats with vigorous-intensity interval exercise training

Melissa A. Linden, Justin A. Fletcher, E. Matthew Morris, Grace M. Meers, M. Harold Laughlin, Frank W. Booth, James R. Sowers, Jamal A. Ibdah, John P. Thyfault, R. Scott Rector

Research output: Contribution to journalArticlepeer-review

62 Scopus citations


Background: There is increasing use of high-intensity interval-type exercise training in the management of many lifestyle-related diseases. Purpose: This study aimed to test the hypothesis that vigorous-intensity interval exercise is as effective as traditional moderate-intensity aerobic exercise training for nonalcoholic fatty liver disease (NAFLD) outcomes in obese, Otsuka Long-Evans Tokushima Fatty (OLETF) rats. Methods: OLETF rats (age, 20 wk; n = 8-10 per group) were assigned to sedentary (O-SED), moderate-intensity exercise training (O-MOD EX; 20 mIminj1, 15% incline, 60 minIdj1, 5 dIwkj1 of treadmill running), or vigorous-intensity interval exercise training (O-VIG EX; 40 mIminj1, 15% incline, 6 × 2.5 min bouts per day, 5 dIwkj1 of treadmill running) groups for 12 wk. Results: Both MOD EX and VIG EX effectively lowered hepatic triglycerides, serum alanine aminotransferase (ALT), perivenular fibrosis, and hepatic collagen 1>1 messenger RNA (mRNA) expression (vs O-SED, P < 0.05). In addition, both interventions increased hepatic mitochondrial markers (citrate synthase activity and fatty acid oxidation) and suppressed markers of de novo lipogenesis (fatty acid synthase, acetyl coenzyme A carboxylase, Elovl fatty acid elongase 6, and steroyl CoA desaturase-1), whereas only MOD EX increased hepatic mitochondrial Beta-hydroxyacyl-CoA dehydrogenase (A-HAD) activity and hepatic triglyceride export marker apoB100 and lowered fatty acid transporter CD36 compared with O-SED.Moreover, whereas total hepatic macrophage population markers (CD68 and F4/80 mRNA) did not differ among groups, MOD EX and VIG EX lowered M1 macrophage polarizationmarkers (CD11c, interleukin-1A, and tumor necrosis factor > mRNA) and MOD EX increasedM2 macrophage marker, CD206 mRNA, compared with O-SED. Conclusions: The accumulation of 15 minIdj1 of VIG EX for 12 wk had similar effectiveness as 60 minIdj1 of MOD EX in the management of NAFLD in OLETF rats. These findings may have important health outcome implications as we work to design better exercise training programs for patients with NAFLD.

Original languageEnglish (US)
Pages (from-to)556-567
Number of pages12
JournalMedicine and science in sports and exercise
Issue number3
StatePublished - Mar 26 2014
Externally publishedYes


  • Nonalcoholic fatty liver disease
  • de novo lipogenesis
  • macrophage polarization
  • mitochondria
  • physical exercise

ASJC Scopus subject areas

  • Orthopedics and Sports Medicine
  • Physical Therapy, Sports Therapy and Rehabilitation


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