Combined effect of canagliflozin and exercise training on high-fat diet-fed mice
Autor: | Hirokazu Takahashi, Kenichi Tanaka, Takanori Iwata, Seiho Nagafuchi, Keizo Anzai, Keiichiro Mine, Kazuki Watanabe, Islam M D Rasadul, Yuichiro Eguchi, Yujin Ohsugi, Kazuyo Sasaki, Sayaka Katagiri |
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Rok vydání: | 2020 |
Předmět: |
Male
medicine.medical_specialty Physiology Endocrinology Diabetes and Metabolism Gene Expression Neovascularization Physiologic Carbohydrate metabolism Diet High-Fat Mice Insulin resistance Non-alcoholic Fatty Liver Disease Physiology (medical) Internal medicine Diabetes mellitus Physical Conditioning Animal Nonalcoholic fatty liver disease Glucose Intolerance Medicine Animals Obesity Canagliflozin Muscle Skeletal Sodium-Glucose Transporter 2 Inhibitors computer.programming_language business.industry sed fungi Fatty liver Body Weight food and beverages Glucose Tolerance Test medicine.disease Mice Inbred C57BL Endocrinology Glucose Adipose Tissue Steatosis Insulin Resistance business computer |
Zdroj: | American journal of physiology. Endocrinology and metabolism. 318(4) |
ISSN: | 1522-1555 |
Popis: | Sodium-glucose cotransporter 2 inhibitors (SGLT2is) have been reported to improve obesity, diabetes, and nonalcoholic fatty liver disease (NAFLD) in addition to exercise training, whereas the combined effects remain to be elucidated fully. We investigated the effect of the combination of the SGLT2i canagliflozin (CAN) and exercise training in high-fat diet-induced obese mice. High-fat diet-fed mice were housed in normal cages (sedentary; Sed) or wheel cages (WCR) with or without CAN (0.03% of diet) for 4 wk. The effects on obesity, glucose metabolism, and hepatic steatosis were evaluated in four groups (Control/Sed, Control/WCR, CAN/Sed, and CAN/WCR). Numerically additive improvements were found in body weight, body fat mass, blood glucose, glucose intolerance, insulin resistance, and the fatty liver of the CAN/WCR group, whereas CAN increased food intake and reduced running distance. Exercise training alone, CAN alone, or both did not change the weight of skeletal muscle, but microarray analysis showed that each resulted in a characteristic change of gene expression in gastrocnemius muscle. In particular, in the CAN/WCR group, there was acceleration of the angiogenesis pathway and suppression of the adipogenesis pathway compared with the CAN/Sed group. In conclusion, the combination of an SGLT2i and exercise training improves obesity, insulin resistance, and NAFLD in an additive manner. Changes of gene expression in skeletal muscle may contribute, at least in part, to the improvement of obesity and insulin sensitivity. |
Databáze: | OpenAIRE |
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