Activation of heat shock response improves biomarkers of NAFLD in patients with metabolic diseases

Abstract

Nonalcoholic fatty liver disease (NAFLD) is often accompanied by metabolic disorders such as metabolic syndrome and type 2 diabetes (T2DM). Heat shock response (HSR) is one of the most important homeostatic abilities but is deteriorated by chronic metabolic insults. Heat shock (HS) with an appropriate mild electrical stimulation (MES) activates HSR and improves metabolic abnormalities including insulin resistance, hyperglycemia and inflammation in metabolic disorders. To analyze the effects o f HS + MES treatment on NAFLD biomarkers, three cohorts including healthy men (two times/week, n = 10), patients with metabolic syndrome (four times/week, n = 40), and patients with T2DM (n = 100; four times/week (n = 40) and two, four, seven times/week (n = 20 each)) treated with HS + MES were retrospectively analyzed. The healthy subjects showed no s ignificant alterations in NAFLD biomarkers after the treatment. In patients with metabolic syndrome, many of the NAFLD steatosis markers, including fatty liver index, NAFLD-liver fat score, liver/spleen ratio and hepatic steatosis index and NAFLD fibrosis marker, asp artate aminotransferase/ alanine aminotransferase (AST/ALT) ratio, were improved upon the treatment. In patients with T2DM, all investigated NAFLD steatosis markers were improv ed and NAFLD fibrosis markers such as the AST/ALT ratio, fibrosis-4 index and NAFLD-fib rosis score were improved upon the treatment. Thus, HS + MES, a physical interve ntion, may become a novel treatment strategy for NAFLD as well as metabolic disorders.

Keywords

• heat shock response (hsr)
• type 2 diabetes (t2dm)
• nonalcoholic fatty liver disease (nafld)
• endoplasmic reticulum (er) stress