The prevalence of primary aldosteronism is much higher than previously thought. Recent studies have shown that primary aldosteronism is related to a higher risk of cardiovascular events. However, the underlying mechanism is not yet clear. Here we investigate the characteristics, including inflammation, fibrosis, and adipokine expression, of adipose tissues from different deposits in patients with aldosterone-producing adenoma (APA). Inflammation and fibrosis changes were evaluated in perirenal and subcutaneous adipose tissues obtained from patients with APA (n = 16), normotension (NT; n = 10), and essential hypertension (EH; n = 5) undergoing laparoscopic surgery. We also evaluated the effect of aldosterone in isolated human perirenal adipose tissue stromal vascular fraction (SVF) cells and investigated the effect of aldosterone in mouse 3T3-L1 and brown preadipocytes. Compared with the EH group, significantly higher levels of interleukin-6 (IL-6) and tumor necrosis factor-α messenger RNA (mRNA) and protein were observed in perirenal adipose tissue of patients with APA. Expression of genes related to fibrosis and adipogenesis in perirenal adipose tissue was notably higher in patients with APA than in patients with NT and EH. Aldosterone significantly induced IL-6 and fibrosis gene mRNA expression in differentiated SVF cells. Aldosterone treatment enhanced mRNA expression of genes associated with inflammation and fibrosis and stimulated differentiation of 3T3-L1 and brown preadipocytes. In conclusion, these data indicate that high aldosterone in patients with APA may induce perirenal adipose tissue dysfunction and lead to inflammation and fibrosis, which may be involved in the high risk of cardiovascular events observed in patients with primary aldosteronism.
BackgroundBrown 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.MethodsDiabetic 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.ResultsCompared 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.ConclusionsActivating BAT could improve kidney injury in diabetic mice via metabolic improvements and renal AMPK activation by beneficial adipokines and miRNAs.
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