Trilobatin Ameliorates Inflammatory Response Through Mir375-Mediated FABP4 Expression In Adipocytes

Abstract Fatty acid binding protein 4 (FABP4) is predominantly expressed in adipose tissue and functions as an important mediator of inflammation. However, small molecules that regulate the expression of FABP4 in adipocytes have not been well characterized. In this work, we found that, together with decreasing the mRNA expression and secretion of proinflammatory cytokines, including tumor necrosis factor α (TNFα) and interleukin -6 (IL-6). Treatment with trilobatin dose-dependently attenuated the mRNA and protein levels of FABP4 in lipopolysaccharide (LPS)-induced differentiated 3T3-L1 adipocytes. Meanwhile, administration of 10 mg/kg trilobatin for 4 weeks (i. g.) also decreased the mRNA and protein levels of FABP4 and the mRNA expression of TNFα and IL-6 in epididymal white adipose tissue (eWAT) and the contents of TNFα and IL-6 in serum of ob/ob mice. In addition, we screened and identified that trilobatin protected against the decrease of microRNA precursors including premiR-375, premiR-338 and premiR-129, but only miR-375 inhibitor prohibited the role of trilobatin on the expression of FABP4, hinted that miR-375 might be involved in trilobatin regulating FABP4 expression in LPS-treated differentiated 3T3-L1 adipocytes. The findings of this study suggested that trilobatin might be a promising compound for the management of obesity because of its anti-inflammatory activity by suppressing the expression of FABP4 in adipocytes.