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

• Main Authors: Zhang Z, Ni L, Zhang L, Zha D, Hu C, Feng H, Wei X, Wu X
• Format: Article
• Language: English
• Published: Dove Medical Press 2021-01-01
• Series: Diabetes, Metabolic Syndrome and Obesity : Targets and Therapy
• Subjects: diabetic nephropathy; empagliflozin; adipor1; p-ampk; p-acc; lipid
• Online Access: https://www.dovepress.com/empagliflozin-regulates-the-adipor1p-ampkp-acc-pathway-to-alleviate-li-peer-reviewed-article-DMSO
• ISSN: 1178-7007

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 [phone]Email [e-mail]: 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