Ipragliflozin Improves Hepatic Steatosis in Obese Mice and Liver Dysfunction in Type 2 Diabetic Patients Irrespective of Body Weight Reduction
| Autor: | Kazuo Kanno, Noriko Shimazu, Chikara Komiya, Kumiko Shiba, Shunsaku Furuke, Shinobu Yamaguchi, Kyoichiro Tsuchiya, Yoshihiro Ogawa, Yasutaka Miyachi |
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| Rok vydání: | 2015 |
| Předmět: |
0301 basic medicine
Leptin Male Steatosis Physiology medicine.medical_treatment Drug Evaluation Preclinical Adipose tissue lcsh:Medicine Mice Obese Gene Expression Pathology and Laboratory Medicine Biochemistry Fats Cytopathology chemistry.chemical_compound Mice 0302 clinical medicine Glucosides Weight loss Non-alcoholic Fatty Liver Disease Animal Cells Medicine and Health Sciences Adipocytes lcsh:Science Connective Tissue Cells Epididymis Multidisciplinary Liver Diseases Fatty liver Organ Size Lipids Adipose Tissue Liver Physiological Parameters Connective Tissue medicine.symptom Cellular Types Anatomy Research Article Adult medicine.medical_specialty 030209 endocrinology & metabolism Thiophenes Gastroenterology and Hepatology Biology Hyperphagia Diet High-Fat 03 medical and health sciences Insulin resistance Sodium-Glucose Transporter 2 Diabetes mellitus Internal medicine Weight Loss medicine Genetics Animals Humans Hypoglycemic Agents Obesity Sodium-Glucose Transporter 2 Inhibitors Insulin lcsh:R Body Weight Biology and Life Sciences Cell Biology medicine.disease Mice Inbred C57BL Fatty Liver 030104 developmental biology Endocrinology Ipragliflozin Glucose Biological Tissue chemistry Diabetes Mellitus Type 2 Anatomical Pathology lcsh:Q Insulin Resistance Energy Intake |
| Zdroj: | PLoS ONE PLoS ONE, Vol 11, Iss 3, p e0151511 (2016) |
| ISSN: | 1932-6203 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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