Exercise training attenuates pulmonary inflammation and mitochondrial dysfunction in a mouse model of high-fat high-carbohydrate-induced NAFLD

Jinkyung Cho, Bruce David Johnson, Kymberly D Watt, Alexander S. Niven, Dongwook Yeo, Chul Ho Kim

Research output: Contribution to journalArticlepeer-review

Abstract

Background: Non-alcoholic fatty liver disease (NAFLD) can lead to pulmonary dysfunction that is associated with pulmonary inflammation. Moreover, little is known regarding the therapeutic role of exercise training on pulmonary pathophysiology in NAFLD. The present study aimed to investigate the effect of exercise training on high-fat high-carbohydrate (HFHC)-induced pulmonary dysfunction in C57BL/6 mice. Methods: Male C57BL/6 mice (N = 40) were fed a standard Chow (n = 20) or an HFHC (n = 20) diet for 15 weeks. After 8 weeks of dietary treatment, they were further assigned to 4 subgroups for the remaining 7 weeks: Chow (n = 10), Chow plus exercise (Chow+EX, n = 10), HFHC (n = 10), or HFHC plus exercise (HFHC+EX, n = 10). Both Chow+EX and HFHC+EX mice were subjected to treadmill running. Results: Chronic exposure to the HFHC diet resulted in obesity with hepatic steatosis, impaired glucose tolerance, and elevated liver enzymes. The HFHC significantly increased fibrotic area (p < 0.001), increased the mRNA expression of TNF-α (4.1-fold, p < 0.001), IL-1β (5.0-fold, p < 0.001), col1a1 (8.1-fold, p < 0.001), and Timp1 (6.0-fold, p < 0.001) in the lung tissue. In addition, the HFHC significantly altered mitochondrial function (p < 0.05) along with decreased Mfn1 protein levels (1.8-fold, p < 0.01) and increased Fis1 protein levels (1.9-fold, p < 0.001). However, aerobic exercise training significantly attenuated these pathophysiologies in the lungs in terms of ameliorating inflammatory and fibrogenic effects by enhancing mitochondrial function in lung tissue (p < 0.001). Conclusions: The current findings suggest that exercise training has a beneficial effect against pulmonary abnormalities in HFHC-induced NAFLD through improved mitochondrial function.

Original languageEnglish (US)
Article number429
JournalBMC Medicine
Volume20
Issue number1
DOIs
StatePublished - Dec 2022

Keywords

  • Exercise
  • Mitochondrial dynamics
  • Mitochondrial function
  • NAFLD
  • Pulmonary inflammation

ASJC Scopus subject areas

  • Medicine(all)

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