Systemic MCPIP1 deficiency in mice impairs lipid homeostasis

Abstract

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.

Role of Mcpip1 in obesity‐induced hepatic steatosis as determined by myeloid and liver‐specific conditional knockouts

“…Similarly to our results, total Mcpip1 knockout mice displayed a decrease in serum levels of HDLcholesterol and total triglycerides, but an increase in LDL/VLDL-cholesterol levels when compared to wildtype mice [34]. As demonstrated here, this phenotype cannot be attributed to Mcpip1 depletion in hepatocytes, since dyslipidemia was detected only in Mcpip1 fl/fl LysM Cre , but not in Mcpip1 fl/fl Alb Cre mice.…”

“…If this process is disturbed, low-density, cholesterol-poor LDL particles lose their affinity to LDL receptors and remain in circulation [35]. High level of LDL-cholesterol in Mcpip1 À/À mice was also explained by the reduced expression of LDL-receptor in hepatocytes [34]. In addition, it was shown that high resistin level-observed also in VAT of myeloid Mcpip1 knockouts-induces degradation of LDL-receptor via PCSK9 protease [36].…”

MCPIP1 alleviates depressive‑like behaviors in mice by inhibiting the TLR4/TRAF6/NF‑κB pathway to suppress neuroinflammation

“…Therefore, new therapeutic biomarkers must be identified. previous studies have reported that MCPIP1 serves important biological roles in lipid homeostasis (30), insulin secretion (31) and the inflammatory response (32), and also regulates the development of certain diseases, such as hidradenitis suppurativa (33), primary biliary cholangitis (34), skin inflammation (35) and clear cell renal cell carcinoma (36). Previous studies have reported that neuroinflammation is a risk factor for depression (42)(43)(44).…”

Rola białka MCPIP1 w metabolizmie lipidów, utrzymaniu homeostazy wątroby oraz rozwoju niealkoholowej stłuszczeniowej choroby wątroby

“…Dyslipidemii w tym modelu towarzyszył spadek masy ciała i tkanki tłuszczowej, który był efektem zwiększenia tempa metabolizmu trójglicerydów w osoczu, zachodzącego na skutek wzrostu poziomu lipazy lipoproteinowej. Ponadto, u tych myszy poziom trójglicerydów w wątrobie był obniżony, w porównaniu do myszy kontrolnych [66]. wzrasta względem komórek kontrolnych (po 24h stymulacji), a następnie obniża się po dłuższej, 9-dniowej inkubacji.…”