Activation of Brown Adipose Tissue Attenuates Diabetic Nephropathy in Mice

Abstract

Brown adipose tissue (BAT) has been regarded as a potential target organ for the treatment of obesity and related metabolic disorders. However, the protective effect of BAT on type 2 diabetic nephropathy (DN) remains unclear. We aimed to test if BAT activation could prevent the development of DN in mice. Type 2 diabetic mice were induced by streptozotocin (STZ) combined with high-fat diet (HFD). CL 316,243, a β3-adrenergic receptor agonist to activate BAT, was administered intraperitoneally (1mg/kg/day) to diabetic mice for 4 weeks. There were no differences in body weight between the groups. Interestingly, the kidney weight and KW/BW ratio were significantly higher in the DM-Con mice compared with the Con and DM+CL mice (p < 0.01). Treatment with CL 316,243 significantly reduced blood glucose and improved dyslipidemia. Simultaneously, activation of BAT led to marked decreases in urinary levels of albumin and 8-hydroxy-deoxyguanosine (8-OH-dG), suppressed fibrotic and inflammatory cytokine synthesis, and finally ameliorated renal morphological abnormalities. In addition to obviously enhancing BAT activity and white adipose tissue (WAT) catabolism, CL 316,243 significantly increased serum adiponectin and the renal sensitivity to FGF-21. Furthermore, the CL 316,243 treatment reactivated the AMPK-SIRT1-PGC1α signaling pathway in kidneys. These findings suggest that activation of BAT attenuates type 2 DN in mice through both the improvement of systemic metabolism and the renoprotective effect of adipokines. Disclosure M. Guan: None. Y. Cai: None. S. Zou: None.