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

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.

Keywords

• high intensity interval training
• skeletal muscle
• liver
• steatosis
• myokines
• matrix metalloproteinases