Kondo Tatsuya, Miyakawa Nobukazu, Kitano Sayaka, Watanabe Takuro, Goto Rieko, Suico Mary Ann, Sato Miki, Takaki Yuki, Sakaguchi Masaji, Igata Motoyuki, Kawashima Junji, Motoshima Hiroyuki, Matsumura Takeshi, Kai Hirofumi, Araki Eiichi
Department of Diabetes, Metabolism and Endocrinology, Kumamoto University Hospital, Chuo-Ward, Kumamoto, Japan.
Department of Metabolic Medicine, Faculty of Life Sciences, Kumamoto University, Chuo-Ward, Kumamoto, Japan.
Endocr Connect. 2021 May 19;10(5):521-533. doi: 10.1530/EC-21-0084.
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 of 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 significant 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, aspartate aminotransferase/alanine aminotransferase (AST/ALT) ratio, were improved upon the treatment. In patients with T2DM, all investigated NAFLD steatosis markers were improved and NAFLD fibrosis markers such as the AST/ALT ratio, fibrosis-4 index and NAFLD-fibrosis score were improved upon the treatment. Thus, HS + MES, a physical intervention, may become a novel treatment strategy for NAFLD as well as metabolic disorders.
非酒精性脂肪性肝病（NAFLD）常伴有代谢综合征和2型糖尿病（T2DM）等代谢紊乱。热休克反应（HSR）是最重要的稳态能力之一，但会因慢性代谢损伤而恶化。适当的轻度电刺激（MES）进行热休克（HS）可激活HSR，并改善代谢紊乱中的代谢异常，包括胰岛素抵抗、高血糖和炎症。为了分析HS + MES治疗对NAFLD生物标志物的影响，对三组人群进行了回顾性分析，包括健康男性（每周两次，n = 10）、代谢综合征患者（每周四次，n = 40）和接受HS + MES治疗的T2DM患者（n = 100；每周四次（n = 40），每周两次、四次、七次（各n = 20））。健康受试者在治疗后NAFLD生物标志物无显著变化。在代谢综合征患者中，许多NAFLD脂肪变性标志物，包括脂肪肝指数、NAFLD肝脏脂肪评分、肝脾比和肝脂肪变性指数以及NAFLD纤维化标志物天冬氨酸氨基转移酶/丙氨酸氨基转移酶（AST/ALT）比值，在治疗后得到改善。在T2DM患者中，所有研究的NAFLD脂肪变性标志物均得到改善，NAFLD纤维化标志物如AST/ALT比值、纤维化-4指数和NAFLD纤维化评分在治疗后也得到改善。因此，HS + MES这种物理干预可能成为NAFLD以及代谢紊乱的一种新的治疗策略。
