The angiotensin converting enzyme 2-angiotensin-(1-7)-Mas axis (ACE2-Ang-(1-7)-Mas axis) is reported to participate in lipid metabolism in kidney, but its precise effects and underlying mechanisms remain unknown. We hypothesized that Ang-(1-7) reduces lipid accumulation and improves renal injury through the low density lipoprotein receptor-sterol regulatory element binding proteins 2-SREBP cleavage activating protein (LDLr-SREBP2-SCAP) system by suppressing inflammation in high fat diet (HFD)-fed mice. In this study, male C57BL/6 mice were randomized into four groups: STD (standard diet)+saline, HFD+saline, HFD+Ang-(1-7) and STD+Ang-(1-7). After 10 weeks of feeding, mice were administered Ang-(1-7) or saline for two weeks. We found that high inflammation status induced by HFD disrupted the LDLr-SREBP2-SCAP feedback system. Treatment of mice fed a high-fat diet with Ang-(1-7) induced significant improvement in inflammatory status, following the downregulation of LDLr, SREBP2 and SCAP, and then, decreased lipid deposition in kidney and improved renal injury. In conclusion, the anti-inflammatory effect of Ang-(1-7) alleviates renal injury triggered by lipid metabolic disorders through a LDLr- SREBP2-SCAP pathway.
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| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4546194 | PMC |
| http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0136187 | PLOS |
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