SGLT2 Inhibition by Empagliflozin Promotes Fat Utilization and Browning and Attenuates Inflammation and Insulin Resistance by Polarizing M2 Macrophages in Diet-induced Obese Mice
| العنوان: | SGLT2 Inhibition by Empagliflozin Promotes Fat Utilization and Browning and Attenuates Inflammation and Insulin Resistance by Polarizing M2 Macrophages in Diet-induced Obese Mice |
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| المؤلفون: | Mayumi Nagashimada, Eric Mayoux, Naoto Nagata, Guanliang Chen, Liang Xu, Shuichi Kaneko, Yinhua Ni, Fen Zhuge, Tsuguhito Ota |
| المصدر: | EBioMedicine EBioMedicine, Vol 20, Iss C, Pp 137-149 (2017) |
| بيانات النشر: | Elsevier BV, 2017. |
| سنة النشر: | 2017 |
| مصطلحات موضوعية: | Male, 0301 basic medicine, HFD, high-fat diet, FGF21, Macrophage, lcsh:Medicine, AST, aspartate aminotransferase, White adipose tissue, 030204 cardiovascular system & hematology, ATMs, adipose tissue macrophages, Brown adipose tissue, EGP, endogenous glucose production, Mice, 0302 clinical medicine, Glucosides, FACS, fluorescence-activated cell sorting, TBARS, thiobarbituric acid reactive substances, Empa, empagliflozin, RER, respiratory exchange ratio, Adiposity, lcsh:R5-920, Glucose tolerance test, medicine.diagnostic_test, NEFA, non-esterified fatty acid, Fatty Acids, CT, computed tomographic, WAT, white adipose tissue, DIO, high-fat-diet-induced obese, General Medicine, TG, triglycerides, Adipose Tissue, H&E, haematoxylin and eosin, GTT, glucose tolerance test, lcsh:Medicine (General), Oxidation-Reduction, Research Paper, NAFLD, non-alcoholic fatty liver disease, medicine.medical_specialty, NASH, non-alcoholic steatohepatitis, Adipose tissue macrophages, Biology, Diet, High-Fat, General Biochemistry, Genetics and Molecular Biology, 03 medical and health sciences, Insulin resistance, VCO2, carbon dioxide production, FGF21, fibroblast growth factor, Internal medicine, UCP1, uncoupling protein 1, medicine, Empagliflozin, Animals, Hypoglycemic Agents, Obesity, Benzhydryl Compounds, Muscle, Skeletal, Sodium-Glucose Transporter 2 Inhibitors, ITT, insulin tolerance test, VO2, oxygen consumption, Inflammation, Macrophages, lcsh:R, SGLT, sodium/glucose cotransporter, Sodium glucose cotransporter-2 inhibitor, Body Weight, Insulin tolerance test, ALT, Alanine aminotransferase, Energy metabolism, UGE, urinary glucose excretion, Macrophage Activation, medicine.disease, BAT, brown adipose tissue, TC, total cholesterol, Fatty Liver, AMPK, AMP-activated protein kinase, Glucose, 030104 developmental biology, Endocrinology, Insulin Resistance, LMs, liver macrophages, Diet-induced obese, Biomarkers |
| الوصف: | 金沢大学医薬保健研究域医学系 Sodium-glucose cotransporter (SGLT) 2 inhibitors increase urinary glucose excretion (UGE), leading to blood glucose reductions and weight loss. However, the impacts of SGLT2 inhibition on energy homeostasis and obesity-induced insulin resistance are less well known. Here, we show that empagliflozin, a SGLT2 inhibitor, enhanced energy expenditure and attenuated inflammation and insulin resistance in high-fat-diet-induced obese (DIO) mice. C57BL/6J mice were pair-fed a high-fat diet (HFD) or a HFD with empagliflozin for 16 weeks. Empagliflozin administration increased UGE in the DIO mice, whereas it suppressed HFD-induced weight gain, insulin resistance, and hepatic steatosis. Moreover, empagliflozin shifted energy metabolism towards fat utilization, elevated AMP-activated protein kinase and acetyl-CoA carbolxylase phosphorylation in skeletal muscle, and increased hepatic and plasma fibroblast growth factor 21 levels. Importantly, empagliflozin increased energy expenditure, heat production, and the expression of uncoupling protein 1 in brown fat and in inguinal and epididymal white adipose tissue (WAT). Furthermore, empagliflozin reduced M1-polarized macrophage accumulation while inducing the anti-inflammatory M2 phenotype of macrophages within WAT and liver, lowering plasma TNFα levels and attenuating obesity-related chronic inflammation. Thus, empagliflozin suppressed weight gain by enhancing fat utilization and browning and attenuated obesity-induced inflammation and insulin resistance by polarizing M2 macrophages in WAT and liver. |
| تدمد: | 2352-3964 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::1c85fd9e3671e9effaeef0acf4b89dd1Test https://doi.org/10.1016/j.ebiom.2017.05.028Test |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....1c85fd9e3671e9effaeef0acf4b89dd1 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 23523964 |
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