PloS one, 2016-03, Vol.11 (3), p.e0151511-e0151511
2016
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- Autor(en) / Beteiligte
- Titel
- Ipragliflozin Improves Hepatic Steatosis in Obese Mice and Liver Dysfunction in Type 2 Diabetic Patients Irrespective of Body Weight Reduction
- Ist Teil von
- PloS one, 2016-03, Vol.11 (3), p.e0151511-e0151511
- Ort / Verlag
- United States: Public Library of Science
- Erscheinungsjahr
- 2016
- Quelle
- Free E-Journal (出版社公開部分のみ）
- Beschreibungen/Notizen
- Type 2 diabetes mellitus (T2DM) is associated with a high incidence of non-alcoholic fatty liver disease (NAFLD) related to obesity and insulin resistance. Currently, medical interventions for NAFLD have focused on diet control and exercise to reduce body weight, and there is a requirement for effective pharmacological therapies. Sodium-glucose cotransporter 2 (SGLT2) inhibitors are oral antidiabetic drugs that promote the urinary excretion of glucose by blocking its reabsorption in renal proximal tubules. SGLT2 inhibitors lower blood glucose independent of insulin action and are expected to reduce body weight because of urinary calorie loss. Here we show that an SGLT2 inhibitor ipragliflozin improves hepatic steatosis in high-fat diet-induced and leptin-deficient (ob/ob) obese mice irrespective of body weight reduction. In the obese mice, ipragliflozin-induced hyperphagia occurred to increase energy intake, attenuating body weight reduction with increased epididymal fat mass. There is an inverse correlation between weights of liver and epididymal fat in ipragliflozin-treated obese mice, suggesting that ipragliflozin treatment promotes normotopic fat accumulation in the epididymal fat and prevents ectopic fat accumulation in the liver. Despite increased adiposity, ipragliflozin ameliorates obesity-associated inflammation and insulin resistance in epididymal fat. Clinically, ipragliflozin improves liver dysfunction in patients with T2DM irrespective of body weight reduction. These findings provide new insight into the effects of SGLT2 inhibitors on energy homeostasis and fat accumulation and indicate their potential therapeutic efficacy in T2DM-associated hepatic steatosis.
- Sprache
- Englisch
- Identifikatoren
- ISSN: 1932-6203eISSN: 1932-6203DOI: 10.1371/journal.pone.0151511Titel-ID: cdi_plos_journals_1773467473
- Format
- –
- Schlagworte
- Accumulation, Adipocytes, Adipose tissue, Adipose Tissue - drug effects, Adipose Tissue - metabolism, Adult, Animals, Antidiabetics, Biology and Life Sciences, Blood glucose, Body fat, Body weight, Body Weight - drug effects, Complications and side effects, Diabetes, Diabetes mellitus, Diabetes Mellitus, Type 2 - complications, Diabetes Mellitus, Type 2 - drug therapy, Diet, High-Fat - adverse effects, Dosage and administration, Drug Evaluation, Preclinical, Drug therapy, Drugs, Endocrinology, Energy balance, Energy intake, Energy Intake - drug effects, Epididymis - drug effects, Epididymis - metabolism, Excretion, Fatty liver, Glucose, Glucose - metabolism, Glucosides - pharmacology, Glucosides - therapeutic use, High fat diet, Homeostasis, Humans, Hyperglycemia, Hyperphagia, Hyperphagia - chemically induced, Hypoglycemic agents, Hypoglycemic Agents - pharmacology, Hypoglycemic Agents - therapeutic use, Inhibitors, Insulin, Insulin Resistance, Kidneys, Laboratory animals, Leptin, Leptin - deficiency, Lipids, Lipids - analysis, Liver, Liver - drug effects, Liver - metabolism, Liver - pathology, Liver cancer, Liver diseases, Male, Medicine and Health Sciences, Metabolism, Mice, Mice, Inbred C57BL, Mice, Obese, Non-alcoholic Fatty Liver Disease - drug therapy, Non-alcoholic Fatty Liver Disease - etiology, Non-alcoholic Fatty Liver Disease - prevention & control, Obesity, Obesity - complications, Organ Size - drug effects, Patients, Pharmacology, Proximal tubules, R&D, Reabsorption, Research & development, Risk factors, Rodents, Sodium, Sodium-glucose cotransporter, Sodium-Glucose Transporter 2 Inhibitors, Steatosis, Thiophenes - pharmacology, Thiophenes - therapeutic use, Type 2 diabetes, Weight Loss, Weight reduction