High intensity interval exercise alters muscle IL-18, FNDC5, and hepatic MMPs in animal model of steatosis: Evidence of skeletal muscle—liver crosstalk

Document Type : Original Article

Authors

1 Young Researchers and Elite Club, Sciences and Researches Branch (Oloom Tahghighat Branch), Islamic Azad University, Tehran, Iran

2 Department of Exercise Physiology, Faculty of Sport Sciences, Alzahra University, Tehran, Iran.

3 Department of Exercise Physiology, Faculty of Physical Education and sport sciences, University of Tehran, Tehran, Iran

4 - KITE Research, Toronto Rehabilitation Institute, University Health Network, Toronto, Canada - Faculty of Kinesiology and Physical Education, University of Toronto, Toronto, Ontario

5 Exercise Physiology Research Center, Lifestyle Institute, Baqiyatallah University of Medical Sciences, Tehran, Iran

6 Department of Biology, Yadegar-e-Imam Khomeini (RAH) Shahre Rey Branch, Islamic Azad University, Tehran, Iran.

Abstract

Steatosis is a common disease worldwide. High intensity interval training (HIIT) may ameliorate steatosis, possibly through interactions between skeletal muscle and liver; however, mechanistic pathways are poorly understood. We aimed to determine potential mechanisms involved in skeletal muscle-liver crosstalk by measuring the gene expression of skeletal muscle interlukin-18 (IL-18) and fibronectin type III domain-containing protein 5 (FNDC5) and hepatic matrix metalloproteinase 2 (MMP-2) and 9 (MMP-9). Thirty-two adult male Wistar rats were randomly divided into four group including normal control (C), high intensity interval training (HIIT), hepatic steatosis+ HIIT (HS+HIIT) and sedentary hepatic steatosis (SHS). HIIT was performed 5 days per week for 5 weeks. Tetracycline (140 mg/kg) was administered by gavage for 7 days to induce NAFLD. We found that HIIT and HS+HIIT increased skeletal muscle expression of FNDC5 relative to SHS group but the increase was attenuated in HS+HIIT. SHS increased muscle IL-18 expression relative to HIIT, HS+HIIT, and C. Expression of hepatic MMP-2 and MMP-9 increased significantly in SHS in comparison with C. There was a significant increase in MMP-9 in HIIT compared with C. Moreover, hepatic MMP-9 expression decreased in both HIIT and SHS+HIIT relative to SHS. MMP-2 decreased significantly in HIIT compared with SHS. Furthermore, muscle IL-18 gene expression was significantly associated with gene expression of hepatic MMP-2 and MMP-9. We conclude that HIIT-induced alteration of skeletal muscle-derived myokines may alter the gene expression of hepatic matrix metalloproteinases, collagenases involved in pathogenesis of liver diseases. Furthermore, steatosis may possibly influence myokine profiles in skeletal muscle. Accordingly, skeletal muscle-liver crosstalk is possibly targeted by HIIT and steatosis in terms of therapeutic approach.

What is already known on this subject?

Exercise training including HIIT improves NAFLD. However, potential HIIT-induced mechanisms, including skeletal muscle-liver crosstalk, are poorly understood.

 

What this study adds?

HIIT may induce skeletal muscle to signal to the liver, improving hepatic steatosis. The outcomes of the present study not only add to body literature of organ-organ crosstalk in chronic disease prevention and treatment, but also help to understand how HIIT-induced signals (myokines) impact the liver, and ultimately mitigate steatosis progression.

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Main Subjects

References

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Journal of Exercise & Organ Cross Talk
Volume 1, Issue 3
December 2021
Pages 115-123

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History

  • Receive Date: 02 October 2021
  • Revise Date: 01 December 2021
  • Accept Date: 15 December 2021

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