Renoprotective effects of brown adipose tissue activation in diabetic mice

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