Renoprotective effects of brown adipose tissue activation in diabetic mice

• Published in: Journal of diabetes 2019-12, Vol.11 (12), p.958-970
• Main Authors: Cai, Ying‐Ying, Zhang, Hong‐Bin, Fan, Cun‐Xia, Zeng, Yan‐Mei, Zou, Shao‐Zhou, Wu, Chun‐Yan, Wang, Ling, Fang, Shu, Li, Ping, Xue, Yao‐Ming, Guan, Mei‐Ping
• Format: Article
• Language: English
• Subjects: adipokine; Adipokines - blood; Adipose Tissue, Brown - drug effects; Adipose Tissue, Brown - metabolism; AMP-Activated Protein Kinases - metabolism; Animals; Blood Glucose - drug effects; Blood Glucose - metabolism; brown adipose tissue; Circulating MicroRNA - blood; CL316,243; Diabetes; Diabetes Mellitus, Experimental - blood; Diabetes Mellitus, Experimental - chemically induced; Diabetes Mellitus, Experimental - drug therapy; Diabetes Mellitus, Type 2 - blood; Diabetes Mellitus, Type 2 - chemically induced; Diabetes Mellitus, Type 2 - drug therapy; diabetic kidney disease; Diabetic Nephropathies - blood; Diabetic Nephropathies - etiology; Diabetic Nephropathies - pathology; Diabetic Nephropathies - prevention & control; Diet, High-Fat; Dioxoles - pharmacology; Hypoglycemic Agents - pharmacology; Kidney - drug effects; Kidney - metabolism; Kidney - pathology; Kidney diseases; Kinases; Lipids - blood; Male; Metabolism; Mice, Inbred C57BL; microRNA; MicroRNAs; Original; Oxidative stress; Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha - metabolism; Signal Transduction; Sirtuin 1 - metabolism; Streptozocin; 棕色脂肪组织; 糖尿病肾脏病; 脂肪因子
• ISSN: 1753-0393; 1753-0407
• DOI: 10.1111/1753-0407.12938

Background Brown adipose tissue (BAT) has been regarded as a potential target organ to combat obesity and related metabolic disorders. However, the effect of BAT activation on the development of diabetic kidney disease (DKD) remains unclear. Methods Diabetic mice were induced by streptozotocin (STZ) combined with a high‐fat diet. To activate BAT, mice were administered 1 mg/kg per day, i.p., CL316,243, a β3‐adrenergic receptor agonist, for 4 weeks. Blood glucose, serum lipids, adipokines, 24‐hour urinary albumin, 8‐hydroxydeoxyguanosine (8‐OHdG), and circulating microRNA (miRNA) levels were analyzed, in addition to renal pathology. Histological changes (fibrosis, inflammation) were evaluated in the kidneys, as was the expression of oxidative stress‐related genes. Renal signaling pathways (fibroblast growth factor [Fgf]21/β‐klotho/FGF receptor 1c and AMP‐activated protein kinase[AMPK]/sirtuin 1 [Sirt1]/peroxisome proliferator‐activated receptor‐γ coactivator‐1α [Pgc1α]) were also evaluated. Results Compared with untreated STZ‐diabetic mice, CL316,243 treatment reduced blood glucose, albeit not significantly (20.58 ± 3.55 vs 23.60 ± 3.90 mM), and significantly decreased triglycerides and low‐density lipoprotein cholesterol and increased high‐density lipoprotein cholesterol. Simultaneously, BAT activation significantly decreased 24‐hour urinary albumin (34.21 ± 6.28 vs 70.46 ± 15.81 μg/24 h; P