Monocyte chemoattractant protein-1 secreted by adipose tissue induces direct lipid accumulation in hepatocytes

Abstract

For many years, adipose tissue has been mainly considered as an inert reservoir for storing triglycerides. Since the discovery that adipocytes may secrete a variety of bioactive molecules (hormones, chemokines, and cytokines), an endocrine and paracrine role for white adipose tissue (WAT) in the regulation of energy balance and other physiological processes has been established, particularly with regard to brain and muscle. In contrast, little is known about the interactions of WAT with liver. Hence, we examined the effect of the secretory products of WAT on hepatocytes. Conditioned medium of human WAT explants induced significant steatosis in hepatocyte cell lines. Factor(s) responsible for the conditioned medium-induced steatosis were screened by a battery of blocking antibodies against different cytokines/chemokines shown to be secreted by WAT. In contrast to interleukin-8 and interleukin-6, the monocyte chemoattractant protein-1 was capable of inducing steatosis in hepatocytes in a time-dependent manner at concentrations similar to those found in conditioned medium. Incubation of conditioned medium with antimonocyte chemoattractant protein-1 antibodies prevented triglyceride accumulation. Investigation of the mechanism leading to the triglyceride accumulation showed that both a diminution of apolipoprotein B secretion and an increase in phosphoenolpyruvate carboxykinase messenger RNA may be involved. Conclusion: The monocyte chemoattractant protein-1 secreted by adipose tissue may induce steatosis not only recruiting macrophages but also acting directly on hepatocytes. (HEPATOLOGY 2008;48:799-807.)

MLK3 promotes metabolic dysfunction induced by saturated fatty acid-enriched diet

“…was demonstrated that MCP-1 is capable of inducing triglyceride accumulation in hepatocytes in vitro in a time-and dose-dependent manner (6). Indeed, we found that diet-induced steatosis was significantly reduced in MLK3-deficient mice (Fig.…”

“…Thus, it has been demonstrated that loss of MCP-1 reduced diet-induced hepatic steatosis, whereas overexpression of MCP1 or incubation of hepatocytes with MCP-1 increased triglyceride accumulation (22). In addition, it was demonstrated that MCP-1, but not IL-6 or IL-8, is capable of inducing triglyceride accumulation in hepatocytes in vitro in a time-and dose-dependent manner (6). Consistent with decreased MCP-1 expression, we observed decreased diet-induced steatosis in MLK3-KO mice (Fig.…”

MCP-1 impacts RCT by repressing ABCA1, ABCG1, and SR-BI through PI3K/Akt posttranslational regulation in HepG2 cells

“…MCP-1 causes cholesterol accumulation in hepatocytes ( 28 ), and HDL receptors in hepatocytes contribute to cholesterol metabolism through the RCT process, including the generation of HDL and cholesterol ester uptake from HDL-cholesterol. Thus, we evaluated the effects of MCP-1 on the activities of HDL receptors in hepatocytes and the this effect was the result of a reduction in the expression of the total protein or in the cell-surface expression of the HDL transporters was unknown.…”

Targeted Overexpression of Inducible 6-Phosphofructo-2-kinase in Adipose Tissue Increases Fat Deposition but Protects against Diet-induced Insulin Resistance and Inflammatory Responses

“…address the direct effects of adipocyte factors generated in response to PFKFB3/iPFK2 overexpression on hepatocyte metabolic and inflammatory responses, adipocyte-conditioned medium was used to treat WT mouse primary hepatocytes as described previously (11,33,34). Palmitate was supplemented into hepatocyte medium to induce fat deposition and inflammatory responses.…”