Empagliflozin Regulates the AdipoR1/p-AMPK/p-ACC Pathway to Alleviate Lipid Deposition in Diabetic Nephropathy

Zhiqin Zhang, Lihua Ni, Lian Zhang, Dongqing Zha, Chun Hu, Lingli Zhang, Huiling Feng, Xiaobao Wei, Xiaoyan Wu Department of Nephrology, Zhongnan Hospital of Wuhan University, Wuhan 430071, People’s Republic of ChinaCorrespondence: Xiaoyan WuDepartment of Nephrology, Zhongnan Hospital of W...

Descripción completa

Guardado en:

Detalles Bibliográficos
Autores principales:	Zhang Z, Ni L, Zhang L, Zha D, Hu C, Feng H, Wei X, Wu X
Formato:	article
Lenguaje:	EN
Publicado:	Dove Medical Press 2021
Materias:	diabetic nephropathy empagliflozin adipor1 p-ampk p-acc lipid Specialties of internal medicine RC581-951
Acceso en línea:	https://doaj.org/article/c6559b1e83804d1083891959214085d3
Etiquetas:	Agregar Etiqueta Sin Etiquetas, Sea el primero en etiquetar este registro!

id	oai:doaj.org-article:c6559b1e83804d1083891959214085d3
record_format	dspace
spelling	oai:doaj.org-article:c6559b1e83804d1083891959214085d32021-12-02T15:20:56ZEmpagliflozin Regulates the AdipoR1/p-AMPK/p-ACC Pathway to Alleviate Lipid Deposition in Diabetic Nephropathy1178-7007https://doaj.org/article/c6559b1e83804d1083891959214085d32021-01-01T00:00:00Zhttps://www.dovepress.com/empagliflozin-regulates-the-adipor1p-ampkp-acc-pathway-to-alleviate-li-peer-reviewed-article-DMSOhttps://doaj.org/toc/1178-7007Zhiqin Zhang, Lihua Ni, Lian Zhang, Dongqing Zha, Chun Hu, Lingli Zhang, Huiling Feng, Xiaobao Wei, Xiaoyan Wu Department of Nephrology, Zhongnan Hospital of Wuhan University, Wuhan 430071, People’s Republic of ChinaCorrespondence: Xiaoyan WuDepartment of Nephrology, Zhongnan Hospital of Wuhan University, Wuhan 430071, People’s Republic of ChinaTel +86 15972935798Email wuxiaoyan2k6@whu.edu.cnBackground: Abnormal lipid deposition in the progress of diabetic nephropathy (DN) plays an important role in a number of studies that have shown that SGLT2 inhibitor (SGLT2i) empagliflozin plays an important role in lipid metabolism, but its mechanism is still unclear.Methods: We aimed to explore the effect of empagliflozin on lipid levels in kidney cancer patients with DN and postoperative patients without DN kidney carcinoma; the patients with DN showed ectopic lipid deposition. In type 2 diabetes model mice induced by streptozotocin (STZ) and a high-fat diet, combined AMPK plus empagliflozin or empagliflozin inhibitor plus compound C was applied, followed by analyses of the blood, urine and kidney indexes to observe the correlation between SGLT2i and AMPK and lipid metabolism in diabetic kidney disease. We determined whether DN in patients with renal tubular atrophy involved lipid metabolism.Results: In clinical specimens, the adiponectin receptor AdipoR1 was reduced, and the phosphorylation acetyl-CoA carboxylase (p-ACC) was increased. In vitro and in vivo pathological immunofluorescence and Western blotting confirmed that, under the condition of high glucose, malpighian tubules displayed ectopic lipid deposition and expressed related lipid parameters accompanied by fibrosis. Empagliflozin intervention reduced lipid deposition fibrosis and renal tubular atrophy, and the addition of compound C promoted disease progression. Moreover, siAdipoR1 transfection proved that AdipoR1 affected P-AMPK and then p-ACC affected lipid metabolism in renal tubular cells.Conclusion: According to the above experimental results, empagliflozin could reduce lipid metabolism of DN through AdipoR1/P-AMPK/P-ACC pathway and delay DN progress.Keywords: diabetic nephropathy, empagliflozin, AdipoR1, p-AMPK, p-ACC, lipidZhang ZNi LZhang LZha DHu CZhang LFeng HWei XWu XDove Medical Pressarticlediabetic nephropathyempagliflozinadipor1p-ampkp-acclipidSpecialties of internal medicineRC581-951ENDiabetes, Metabolic Syndrome and Obesity: Targets and Therapy, Vol Volume 14, Pp 227-240 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	diabetic nephropathy empagliflozin adipor1 p-ampk p-acc lipid Specialties of internal medicine RC581-951
spellingShingle	diabetic nephropathy empagliflozin adipor1 p-ampk p-acc lipid Specialties of internal medicine RC581-951 Zhang Z Ni L Zhang L Zha D Hu C Zhang L Feng H Wei X Wu X Empagliflozin Regulates the AdipoR1/p-AMPK/p-ACC Pathway to Alleviate Lipid Deposition in Diabetic Nephropathy
description	Zhiqin Zhang, Lihua Ni, Lian Zhang, Dongqing Zha, Chun Hu, Lingli Zhang, Huiling Feng, Xiaobao Wei, Xiaoyan Wu Department of Nephrology, Zhongnan Hospital of Wuhan University, Wuhan 430071, People’s Republic of ChinaCorrespondence: Xiaoyan WuDepartment of Nephrology, Zhongnan Hospital of Wuhan University, Wuhan 430071, People’s Republic of ChinaTel +86 15972935798Email wuxiaoyan2k6@whu.edu.cnBackground: Abnormal lipid deposition in the progress of diabetic nephropathy (DN) plays an important role in a number of studies that have shown that SGLT2 inhibitor (SGLT2i) empagliflozin plays an important role in lipid metabolism, but its mechanism is still unclear.Methods: We aimed to explore the effect of empagliflozin on lipid levels in kidney cancer patients with DN and postoperative patients without DN kidney carcinoma; the patients with DN showed ectopic lipid deposition. In type 2 diabetes model mice induced by streptozotocin (STZ) and a high-fat diet, combined AMPK plus empagliflozin or empagliflozin inhibitor plus compound C was applied, followed by analyses of the blood, urine and kidney indexes to observe the correlation between SGLT2i and AMPK and lipid metabolism in diabetic kidney disease. We determined whether DN in patients with renal tubular atrophy involved lipid metabolism.Results: In clinical specimens, the adiponectin receptor AdipoR1 was reduced, and the phosphorylation acetyl-CoA carboxylase (p-ACC) was increased. In vitro and in vivo pathological immunofluorescence and Western blotting confirmed that, under the condition of high glucose, malpighian tubules displayed ectopic lipid deposition and expressed related lipid parameters accompanied by fibrosis. Empagliflozin intervention reduced lipid deposition fibrosis and renal tubular atrophy, and the addition of compound C promoted disease progression. Moreover, siAdipoR1 transfection proved that AdipoR1 affected P-AMPK and then p-ACC affected lipid metabolism in renal tubular cells.Conclusion: According to the above experimental results, empagliflozin could reduce lipid metabolism of DN through AdipoR1/P-AMPK/P-ACC pathway and delay DN progress.Keywords: diabetic nephropathy, empagliflozin, AdipoR1, p-AMPK, p-ACC, lipid
format	article
author	Zhang Z Ni L Zhang L Zha D Hu C Zhang L Feng H Wei X Wu X
author_facet	Zhang Z Ni L Zhang L Zha D Hu C Zhang L Feng H Wei X Wu X
author_sort	Zhang Z
title	Empagliflozin Regulates the AdipoR1/p-AMPK/p-ACC Pathway to Alleviate Lipid Deposition in Diabetic Nephropathy
title_short	Empagliflozin Regulates the AdipoR1/p-AMPK/p-ACC Pathway to Alleviate Lipid Deposition in Diabetic Nephropathy
title_full	Empagliflozin Regulates the AdipoR1/p-AMPK/p-ACC Pathway to Alleviate Lipid Deposition in Diabetic Nephropathy
title_fullStr	Empagliflozin Regulates the AdipoR1/p-AMPK/p-ACC Pathway to Alleviate Lipid Deposition in Diabetic Nephropathy
title_full_unstemmed	Empagliflozin Regulates the AdipoR1/p-AMPK/p-ACC Pathway to Alleviate Lipid Deposition in Diabetic Nephropathy
title_sort	empagliflozin regulates the adipor1/p-ampk/p-acc pathway to alleviate lipid deposition in diabetic nephropathy
publisher	Dove Medical Press
publishDate	2021
url	https://doaj.org/article/c6559b1e83804d1083891959214085d3
work_keys_str_mv	AT zhangz empagliflozinregulatestheadipor1pampkpaccpathwaytoalleviatelipiddepositionindiabeticnephropathy AT nil empagliflozinregulatestheadipor1pampkpaccpathwaytoalleviatelipiddepositionindiabeticnephropathy AT zhangl empagliflozinregulatestheadipor1pampkpaccpathwaytoalleviatelipiddepositionindiabeticnephropathy AT zhad empagliflozinregulatestheadipor1pampkpaccpathwaytoalleviatelipiddepositionindiabeticnephropathy AT huc empagliflozinregulatestheadipor1pampkpaccpathwaytoalleviatelipiddepositionindiabeticnephropathy AT zhangl empagliflozinregulatestheadipor1pampkpaccpathwaytoalleviatelipiddepositionindiabeticnephropathy AT fengh empagliflozinregulatestheadipor1pampkpaccpathwaytoalleviatelipiddepositionindiabeticnephropathy AT weix empagliflozinregulatestheadipor1pampkpaccpathwaytoalleviatelipiddepositionindiabeticnephropathy AT wux empagliflozinregulatestheadipor1pampkpaccpathwaytoalleviatelipiddepositionindiabeticnephropathy
_version_	1718387421407608832

Empagliflozin Regulates the AdipoR1/p-AMPK/p-ACC Pathway to Alleviate Lipid Deposition in Diabetic Nephropathy

Ejemplares similares