Atherosclerosis involves interactions between inflammation system and dyslipidemia. MCPIP1 (Monocyte Chemotactic Protein induced Protein-1) is induced by proinflammatory molecules and serves as a negative feedback loop in regulating inflammatory responses. Our current study was designed to test the role of MCPIP1 in maintaining lipid homeostasis, the latter a pivotal factor that contributes to the pathogenesis of atherosclerosis. We found that MCPIP1 knockout mice displayed a decrease in levels of serum HDL-cholesterol and total triglycerides but an increase in serum LDL/VLDL-cholesterol levels when compared to wild-type mice. Additionally, ApoA-1 expression was reduced but LPL expression was upregulated in plasma from MCPIP1 knockout mice. The livers from the MCPIP1 knockout mice revealed a decrease in hepatocyte number and an increase in collagen deposition when compared to wild-type mice. These findings suggest that MCPIP1 deficiency can induce liver fibrosis, alter the expression of lipoproteins, and affect transportation and metabolism of lipids, indicating that MCPIP1 is involved in maintaining lipid homeostasis, possibly via negatively regulating inflammatory responses.
Background:Increased inflammation is associated with alterations of lipid and lipoprotein metabolism. Recent studies suggest that MCPIP1 (Monocyte Chemotactic Protein induced Protein‐1) may have a role in maintaining normal metabolic balance by negatively regulating chronic inflammation. Our preliminary data revealed that the MCPIP1 deficient (MCPIP1‐/‐) mice have reduced body lipid deposits compared to control mice. The current project was designed to test if MCPIP1 is involved in maintaining lipid homeostasis by affecting hepatic lipid production and distribution. Methods: MCPIP1‐/‐ mice (C57/BL6 background, 6 weeks old) were identified by PCR. The serum and liver from control and MCPIP1‐/‐ mice were collected after fasting. Serum lipids (LDL/VLDL‐cholesterol and total triglyceride) and liver lipids (total cholesterol and triglyceride) were measured using commercially available kits. Results: The data collected from sixteen samples (eight control and eight MCPIP1‐/‐) showed that in MCPIP1 ‐/‐ mice the mean serum HDL‐cholesterol and total triglyceride concentrations were about 49% and 31% lower respectively, compared to control mice. In contrast, serum concentration of LDL/VLDL‐cholesterol in MCPIP1‐/‐ mice increased about 66% when compared to control. Triglyceride in the liver tissue of MCPIP‐/‐ mice was also drastically decreased (72% lower than control). No changes were observed in total cholesterol in liver tissue. Conclusion: The lack of MCPIP1 is associated with alterations of lipid homeostasis. Grant Funding Source: Supported by KCOM Graduate Program in Biomedical Sciences
BackgroundMonocyte chemotactic protein‐induced protein 1 (MCPIP1) is found in monocytes/macrophages in response to MCP‐1 stimulation. Our preliminary data showed that MCPIP1 knockout mice have increased plasma LDL cholesterol and decreased HDL and total triglycerides. We have also found that mice lacking MCPIP1 display a marked loss of adipose and muscle tissues. Our current project was designed to determine whether MCPIP1‐deficiency impairs lipid homeostasis by affecting the apoprotein expression hepatic remodeling.MethodsC57/BL6 mice at 6‐8 weeks of age were used. Liver histological changes and plasma apoprotein expression were examined in samples collected from wild‐type, heterozygous, and MCPIP1 knockout mice.Resultshepatic histological staining revealed an increase in collagen and fibrous tissue and a decrease in hepatocytes in MCPIP1 knockout mice. We also found that the expression of LPL, and apoB48 is increased but the apoB100 and apoA‐1 is decreased in the plasma from MCPIP1 knockout mice.ConclusionsThe data collected so far suggest that the impaired lipid homeostasis observed in MCPIP1 deficient mice may occur through hepatic remodeling and alteration of apoprotein expression and/or function.
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