Resveratrol increases AdipoR1 and AdipoR2 expression in type 2 diabetic nephropathyReportar como inadecuado




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Journal of Translational Medicine

, 14:176

Cardiovascular, Metabolic and Lipoprotein Translation

Abstract

BackgroundAdiponectin has multiple functions including insulin sensitization, anti-inflammation and antiatherogenesis in various organs. Adiponectin activates 5′-adenosine monophosphate-activated protein kinase AMPK and peroxisome proliferator-activated receptor PPARα via the adiponectin receptor AdipoR 1 and 2, which are critical for regulating lipids and glucose homeostasis and for controlling oxidative stress. We investigated whether resveratrol can inhibit renal damage in type 2 diabetic db-db mice and the underlying mechanisms of its effects.

MethodsFour groups of male C57 BLKS-J db-m and db-db mice and human glomerular endothelial cells HGECs were used. Resveratrol was administered to diabetic and nondiabetic mice by oral gavage for 12 weeks starting at 8 weeks of age.

ResultsIn db-db mice, resveratrol increased serum adiponectin levels and decreased albuminuria, glomerular matrix expansion, inflammation and apoptosis in the glomerulus. Resveratrol increased the phosphorylation of AMPK and silent information regulator T1 SIRT1, and decreased phosphorylation of downstream effectors class O forkhead box FoxO1 and FoxO3a via increasing AdipoR1 and AdipoR2 in the renal cortex. Furthermore, resveratrol increased expression of PPARγ coactivator PGC-1α, estrogen-related receptor-1α, and phosphorylated acetyl-CoA carboxylase and decreased sterol regulatory element-binding protein 1. This effect lowered the content of nonesterified fatty acid and triacylglycerol in the kidneys, decreasing apoptosis, oxidative stress and activating endothelial nitric oxide synthase. Resveratrol prevented cultured HGECs from undergoing high-glucose-induced oxidative stress and apoptosis by activating the AMPK–SIRT1–PGC–1α axis and PPARα through increases in AdipoR1 and AdipoR2 expression.

ConclusionsThese results suggest that resveratrol prevents diabetic nephropathy by ameliorating lipotoxicity, oxidative stress, apoptosis and endothelial dysfunction via increasing AdipoR1 and AdipoR2 expression.

KeywordsAdiponectin 5′-adenosine monophosphate-activated protein kinase Diabetic nephropathy Resveratrol AbbreviationsAMPK5′-adenosine monophosphate-activated protein kinase

AdipoRadiponectin receptor

BaxBcl-2-associated X protein

Bcl-2B cell leukemia-lymphoma 2

CKDchronic kidney disease

CMCcarboxymethyl cellulose sodium salt

Col IVtype IV collagen

DAPI4,6-diamidino-2-phenylindole

DMdiabetes mellitus

DNdiabetic nephropathy

eNOSendothelial nitric oxide synthase

ERRestrogen-related receptor

8-epi-PGF28-epi-prostaglandin F2

8-OH-dG8-hydroxy-2-deoxyguanosine

FoxOclass O forkhead box

HbA1chemoglobin A1c

HGEChuman glomerular endothelial cell

NEFAnonesterified fatty acid

pACCphosphorylated acetyl-CoA carboxylase

PASperiodic acid–Schiff

PBSphosphate buffered saline

PGCPPARγ coactivator

PPARperoxisome proliferator-activated receptor

siRNAsmall interfering RNA

SIRT1silent information regulator T1

SREBPsterol regulatory element-binding protein

TGtriacylglycerol

TGF-β1transforming growth factor-β1

TUNELterminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling

Electronic supplementary materialThe online version of this article doi:10.1186-s12967-016-0922-9 contains supplementary material, which is available to authorized users.

An erratum to this article can be found at http:-dx.doi.org-10.1186-s12967-016-0967-9.

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Autor: Hoon Suk Park - Ji Hee Lim - Min Young Kim - Yaeni Kim - You Ah Hong - Sun Ryoung Choi - Sungjin Chung - Hyung Wook 

Fuente: https://link.springer.com/







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