activation significantly decreased 24-hour urinary albumin from 70.46 ± 15.81 μg/24 h to 34.21 ± 6.28 μg/24 h (P < 0.05) in diabetic mice.
Activation of brown adipose tissue (BAT) reduced blood glucose levels, showing a decrease from 23.60 ± 3.90 mM to 20.58 ± 3.55 mM, although this was not statistically significant.
Triglycerides and low-density lipoprotein cholesterol levels were significantly decreased, while high-density lipoprotein cholesterol levels increased following BAT activation.
Renal pathology showed improvements, with reduced fibrosis, inflammation, and oxidative stress in the kidneys of treated diabetic mice.
CL316,243 treatment enhanced serum adiponectin levels and renal sensitivity to Fgf21, indicating metabolic benefits.
The treatment also activated the renal AMPK/Sirt1/Pgc1α signaling pathway and influenced the levels of circulating microRNAs and their target gene expression in the kidneys.
Simplified
BACKGROUND: (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 (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 β-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. 3
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 < 0.05) and 8-OHdG, improved renal fibrosis, inflammation, and oxidative stress, and ameliorated renal morphological abnormalities. In addition to enhancing BAT activity, CL316,243 significantly increased serum adiponectin concentrations and renal Fgf21 sensitivity, and reactivated the renal AMPK/Sirt1/Pgc1α signaling pathway. Furthermore, CL316,243 treatment increased levels of some circulating miRNAs and downregulated expression of their target genes in the kidney.
CONCLUSIONS: Activating BAT could improve kidney injury in diabetic mice via metabolic improvements and renal AMPK activation by beneficial adipokines and miRNAs.
Key numbers
34.21 ± 6.28 μg/24 h
Decrease in Urinary Albumin Excretion
Urinary albumin levels in diabetic mice treated with CL316,243.
0.53 ± 0.02 mM
Triglycerides Reduction
Triglyceride levels in diabetic mice after activation.
Not quantified
Restoration of Serum Adiponectin
Serum adiponectin concentrations in diabetic mice treated with CL316,243.
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