Telmisartan Ameliorates Nephropathy in Metabolic Syndrome by Reducing Leptin Release From Perirenal Adipose Tissue.
Metabolic syndrome (MetS) is associated with nephropathy. Along with common risk factors such as hypertension and hyperglycemia, adipocytokines released from perirenal adipose tissue (PRAT) are implicated in the pathogenesis of MetS nephropathy. The study was designed to elucidate the adverse effects of PRAT-derived leptin on nephropathy and to determine whether the angiotensin II type 1 receptor antagonist telmisartan exerts a renoprotective effect by decreasing the PRAT-derived leptin level in the high-fat diet-induced MetS rat. In MetS rats, PRAT-derived leptin expression increased concomitant with dysfunction of adipogenesis, and the activities of the angiotensin II-angiotensin II type 1 receptor and the angiotensin-converting enzyme 2-angiotensin (1-7)-Mas receptor axes were imbalanced in PRAT. PRAT-derived leptin from MetS rats promoted proliferation of rat glomerular endothelial cells (GERs) by activating the p38 MAPK (mitogen-activated protein kinase) pathway, thereby contributing to the development of nephropathy. Long-term telmisartan treatment improved metabolic parameters and renal function, decreased the amount of PRAT, promoted adipogenesis, increased the expression of angiotensin-converting enzyme 2, restored balanced activities of the angiotensin II-AT1R and angiotensin-converting enzyme 2-angiotensin (1-7)-Mas axes, and exerted an indirect renoprotective effect on MetS rats by decreasing PRAT-derived leptin release. Our results demonstrate a novel link between nephropathy and PRAT in MetS and show that telmisartan confers an underlying protective effect on visceral adipose tissue and the kidney, suggesting that it has potential as a therapeutic agent for the treatment of MetS-associated nephropathy.
['Li|Hao|H|', 'Li|Min|M|', 'Liu|Ping|P|', 'Wang|YaPing|Y|', 'Zhang|Heng|H|', 'Li|HongBin|H|', 'Yang|ShiFeng|S|', 'Song|Yan|Y|', 'Yin|YanRong|Y|', 'Gao|Lan|L|', 'Cheng|Si|S|', 'Cai|Jun|J|', 'Tian|Gang|G|']
D050156:Adipogenesis D047228:Angiotensin II Type 1 Receptor Blockers D000818:Animals D001562:Benzimidazoles D001565:Benzoates D004195:Disease Models, Animal D050152:Intra-Abdominal Fat D007674:Kidney Diseases D020738:Leptin D008297:Male D024821:Metabolic Syndrome D020011:Protective Agents D051381:Rats D017208:Rats, Wistar D000077333:Telmisartan
telmisartan leptin angiotensin-converting enzyme 2 adipocytes obesity