The Effects And Mechanism Of Ursolic Acid On Inflammation And Lipid Metabolism In Adipocytes

Adipose tissue,which regulates lipid metabolism and also secretes inflammatory cytokines,is an important organ for maintaining metabolic homeostasis.Ursolic acid(UA)shows its role in regulation of inflammatory gene expression in macrophages,skin and colonic mucosal tissue,however,it is not known whether the expression of those genes were regulated by UA in adipocytes.This study aims to evaluate the effects and mechanism of UA on inflammation and lipid metabolism in adipocytes,which was investigated through in vivo and vitro experiments.Experiment Ⅰ The effects UA on inflammation and lipid metabolism in adipocytesMature adipocytes were stimulated by UA in a dose(0,10,25 and 50 μM)or time(0,6,12 and 24 h)gradient manner.Collecting the cells and culture medium,then evaluating the levels of inflammatory cytokine secretion and the m RNA expression of inflammatory cytokine genes and lipid metabolism genes.The results indicated that: In different gradient of UA concentration experiments,compared to the control group,The expression of IL-6,MCP-1 and MCP-3 were significantly increased by 10,25 and 50 μM UA for 12 h,however,The level of IL-6 in culture medium was notably elevated only by 10 μM UA;Besides,the expression of TLR4 was significantly elevated by 25 and 50 μM UA.In different gradient of time experiments,compared to the control group,the expression of IL-6,MCP-1,MCP-3and TLR4 were significantly increased by 25 μM UA for 6,12 and 24 h,meanwhile,the expression of IKKβ was notably upgraded by 25 μM UA for 12 and 24 h.Further research showed that the phosphorylation levels of p-ERK and p-NF-κB were significantly increased by 25 μM UA for 30 and 60 min;The expression of SREBP1 c,ACC1 and FAS were inhibited by UA,but the expression of FOXO1 and ATGL was considerably up-regulated by UA.Besides,the level of ACC protein was also significantly diminished by UA.Experiment Ⅱ The effects of UA on inflammation and lipid metabolism in adipose tissueThirteen 12-year-old mice with the similar weight were compartmentalized into 2 groups.one of the groups was intraperitoneal injected with 20 mg/kg BW UA(n=6);the rest of them were injected with the control solution(n=7).These objects were injected once daily for 4days.The results showed that: compared to the control group,the body weight gain was significant decreased by UA,besides,the relative weight of spleen tissue had tended to lose under the action of UA;Furthermore,UA had significantly increased the expression of IL-6,TLR4 and MCP-1 in epididymal fat tissue as well as the content of MCP-1 in serum,but the expression of FGF21 was significantly decreased by UA.Meanwhile,the number of CD14 monocytes were significantly increased by UA in epididymal fat tissueIn summary: The process that UA stimulated the expression and secretion of IL-6 may be mainly regulated by TLR4/IKKβ/NF-κB or ERK/NF-κB signaling pathways in adipocytes.Besides,UA also showed its function on inhibition of adipogenesis and promotion of lipolysis in adipocytes.Furthermore,UA inhibited the protein expression of ACC and stimulated the expression of ATGL,which may be mainly regulated by FOXO1/SREBP1 c and FOXO1/ATGL signaling pathways.In vivo,UA recruited CD14 monocytes possibly by up-regulation of the expression and secretion of MCP-1 in adipose tissue.