Angiotensin-(1-7) Ameliorates High Fat Diet-induced Renal Injury Via Anti-inflammatory Activity In Mice

Objective: It is reported that the angiotensin converting enzyme2-angiotensin-(1-7)-Mas axis(ACE2-Ang-(1-7)-Mas axis) participate in lipid metabolism in kidney, however its definite effects and potential mechanisms remain unknown. We supposed that Ang-(1-7) play an anti-inflammatory role in alleviating renal injury induced by lipid metabolic disorders through a LDLr- SREBP2-SCAP pathway in high fat diet(HFD)-fed mice.Methods: 40 Male C57BL/6 mice were divided into four groups,randomly: STD(standard diet)+saline, HFD+saline, HFD+Ang-(1-7) and STD+Ang-(1-7). After 10 weeks of feeding, mice were injected saline or Ang-(1-7)(144ug/kg·day)for two weeks. Blood was collected to measure serum TC, TG, LDL, BUN, Scr, CRP, TNF-α, IL-6 levels, and urine samples collected for assessment of urinary albumin. The renal structure was examined via hematoxylin-eosin(HE) staining and transmission electron microscopy(TEM). Expression levels of LDLr, SCAP, SREBP-2,TNF-α, IL-6 and MCP-1 in kidney were evaluated usingimmunohistochemical, real-time PCR and Western blot analyses. Lipid deposition in kidney was detected with Oil Red O staining. The renal cholesterol content was measured via enzymatic assay.Results: High inflammation status induced by HFD disrupted the LDLr-SREBP2-SCAP feedback system. Treatment with Ang-(1-7) in high-fat diet mice induced distinct improvement in inflammatory status.HFD induced lipid metabolism disorders and renal injury in mice.Treatment with Ang-(1-7) in high-fat diet mice lead to a downregulation of LDLr, SREBP2 and SCAP, and then, reduced lipid deposition in renal tissue and ameliorated renal injury.Conclusions:(1) HFD can induce high inflammation status, lipid metabolism disorders and renal injury in mice.(2) High inflammation status induced by HFD disrupted the LDLr-SREBP2-SCAP feedback system.(3) It is the first time to prove that Ang-(1-7) play an anti-inflammtory role in improving renal injury induced by disturbance of lipid metabolism through a LDLr- SREBP2-SCAP pathway.