Background: Nonalcoholic fatty liver disease (NAFLD) often accompanies with metabolic disorders, such as metabolic syndrome (Mets) and type 2 diabetes (T2D). Effective treatment strategy to control NAFLD is not fully established yet. Cellular stress adaptation is one of the most important homeostatic ability, but this response can be deteriorated by metabolic insults. Heat shock (HS) with appropriate mild electrical stimulation (MES) activates stress adaptive heat shock response and improves metabolic abnormalities such as insulin resistance, hyperglycemia and inflammation in Mets and T2D.

Methods: Retrospective analysis of the effects of MES+HS treatment on NAFLD biomarkers was performed in the subject with healthy men (n=10), Mets (n=40) and the patient with T2D (n=100).

Results: In healthy males, there were no alterations in NAFLD steatosis or fibrosis biomarkers. In subjects with Mets, many of the NAFLD steatosis markers, such as AST/ALT ratio (from 0.80 to 0.94. p<0.01), fatty liver index (FLI: from 62.3 to 57.3. p<0.01), NAFLD-liver fat score (NAFLD-LFS: from 0.002 to - 0.276. p<0.01), liver/spleen (L/S) ratio (from 0.994 to 1.098. p<0.01) and hepatic steatosis index (HSI: from 37.2 to 36.0. p<0.01) were ameliorated upon MES+HS treatment, but NAFLD fibrosis markers were not. In patients with T2D, all those investigated NAFLD steatosis markers including AST/ALT ratio (from 0.94 to 1.08. p<0.05), FLI (from 64.0 to 59.6. p<0.01), LFS (from 1.40 to 0.90. p<0.05), L/S ratio (from 0.987 to 1.096. p<0.01) and HSI (from 40.2 to 39.4. p<0.01), visceral adiposity index (VAI: from 219.4 to 197.2. p<0.01) and triglyceride × fasting glucose index (TyG: from 4.05 to 3.95. p<0.01) were improved and NAFLD fibrosis markers such as Fib4 index (from 1.72 to 1.62. p<0.05) and NAFLD-fibrosis score (from - 0.23 to - 0.18. p<0.05) were ameliorated upon MES+HS treatment.

Conclusions: Thus MES+HS, a physical interventional medicine may become a novel treatment strategy for NAFLD as well as metabolic disorders.


T. Kondo: None. S. Kitano: None. N. Miyakawa: None. T. Watanabe: None. R. Goto: None. M. Sakaguchi: None. M. Igata: None. J. Kawashima: None. H. Motoshima: None. T. Matsumura: None. E. Araki: Advisory Panel; Self; Abbott. Speaker’s Bureau; Self; ARKRAY, Astellas Pharma Inc., AstraZeneca, Eli Lilly Japan K.K., Merck & Co., Inc., Novo Nordisk Inc., WebMD LLC. Other Relationship; Self; Kowa Company, Ltd., Mitsubishi Tanabe Pharma Corporation, Novartis Pharma K.K., Sumitomo Dainippon Pharma Co., Ltd., Takeda Pharmaceutical Company Limited.


Japan Ministry of Economy, Trade and Industry (24-065)

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