Abstract
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.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Acute Kidney Injury / drug therapy*
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Acute Kidney Injury / etiology
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Acute Kidney Injury / immunology
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Acute Kidney Injury / pathology
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Angiotensin I / pharmacology
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Angiotensin I / therapeutic use*
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Animals
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Anti-Inflammatory Agents / pharmacology
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Anti-Inflammatory Agents / therapeutic use*
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Diet, High-Fat / adverse effects*
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Dyslipidemias / drug therapy
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Dyslipidemias / etiology
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Dyslipidemias / immunology
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Dyslipidemias / pathology
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Inflammation / drug therapy
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Inflammation / etiology
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Inflammation / immunology
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Inflammation / pathology
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Kidney / drug effects
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Kidney / immunology
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Kidney / pathology
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Lipid Metabolism / drug effects
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Male
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Mice, Inbred C57BL
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Peptide Fragments / pharmacology
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Peptide Fragments / therapeutic use*
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Receptors, LDL / immunology*
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Signal Transduction / drug effects
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Sterol Regulatory Element Binding Protein 2 / immunology*
Substances
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Anti-Inflammatory Agents
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Peptide Fragments
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Receptors, LDL
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Sterol Regulatory Element Binding Protein 2
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Angiotensin I
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angiotensin I (1-7)
Grants and funding
This work was conducted using grants from the National Natural Science Youth Foundation of China (NO. 81200519, Lin Tang). The funder was the main study designer and participated in preparation of the manuscript.