Among the four prostaglandin E2 receptors,EP3 receptor is the one most abundantly expressed in white adipose tissue(WAT).The mouse EP3 gene gives rise to three isoforms,namely EP3α,EP3β,and EP3γ,which differ only a...Among the four prostaglandin E2 receptors,EP3 receptor is the one most abundantly expressed in white adipose tissue(WAT).The mouse EP3 gene gives rise to three isoforms,namely EP3α,EP3β,and EP3γ,which differ only at their C-terminal tails.To date,functions of EP3 receptor and its isoforms in WAT remain incompletely characterized.In this study,we found that the expression of all EP3 isoforms were downregulated in WAT of both db/db and high-fat diet-induced obese mice.Genetic ablation of three EP3 receptor isoforms(EP3^(−/−)mice)or EP3αand EP3γisoforms with EP3βintact(EP3βmice)led to an obese phenotype with increased food intake,decreased motor activity,reduced insulin sensitivity,and elevated serum triglycerides.Since the differentiation of preadipocytes and mouse embryonic fibroblasts to adipocytes was markedly facilitated by either pharmacological blockade or genetic deletion/inhibition of EP3 receptor via the cAMP/PKA/PPARγpathway,increased adipogenesis may contribute to obesity in EP3^(−/−)and EP3βmice.Moreover,both EP3^(−/−)and EP3βmice had increased lipolysis in WAT mainly due to the activated cAMP/PKA/hormone-sensitive lipase pathway.Taken together,our findings suggest that EP3 receptor and itsαandγisoforms are involved in both adipogenesis and lipolysis and influence food intake,serum lipid levels,and insulin sensitivity.展开更多
[目的]检测前列腺素E2(prostaglandin E2,PGE2)通过G蛋白偶联前列腺素E受体1(prostaglandin E re-ceptor1,EP1)对腰椎软骨终板细胞生长的影响。[方法]常规方法培养腰椎软骨终板细胞;应用RT-PCR和蛋白免疫印迹技术检测细胞EP基因及蛋白...[目的]检测前列腺素E2(prostaglandin E2,PGE2)通过G蛋白偶联前列腺素E受体1(prostaglandin E re-ceptor1,EP1)对腰椎软骨终板细胞生长的影响。[方法]常规方法培养腰椎软骨终板细胞;应用RT-PCR和蛋白免疫印迹技术检测细胞EP基因及蛋白质表达水平。应用MTT实验评估EP1受体选择性激动剂17-P-T-PGE2和EP1受体选择性抑制剂SC 51322对细胞生长增殖的影响。[结果]RT-PCR和Western blotting实验检测结果表明,软骨终板细胞均表达EP1、EP2、EP3和EP4。MTT实验检测显示EP1受体激动剂17-P-T-PGE2可促进软骨终板细胞生长,EP1受体选择性抑制剂SC 51322可抑制PGE2促起的软骨终板细胞生长。[结论]PGE2引起的软骨终板细胞增殖可能与EP1信号转导通路激活相关。展开更多
基金supported by the National Basic Research Program of China(973 Program)(2012CB517504 to Y.-F.G.)the National Natural Science Foundation of China(81390351,81270275,81200511,and 81030003 to Y.-F.G.)+1 种基金National Institutes of Health grants(DK46205 to R.M.B.)the Swedish Research Council(to J.-A.G.),and Shenzhen Peacock Plan&JCYJ 20140418095735626.
文摘Among the four prostaglandin E2 receptors,EP3 receptor is the one most abundantly expressed in white adipose tissue(WAT).The mouse EP3 gene gives rise to three isoforms,namely EP3α,EP3β,and EP3γ,which differ only at their C-terminal tails.To date,functions of EP3 receptor and its isoforms in WAT remain incompletely characterized.In this study,we found that the expression of all EP3 isoforms were downregulated in WAT of both db/db and high-fat diet-induced obese mice.Genetic ablation of three EP3 receptor isoforms(EP3^(−/−)mice)or EP3αand EP3γisoforms with EP3βintact(EP3βmice)led to an obese phenotype with increased food intake,decreased motor activity,reduced insulin sensitivity,and elevated serum triglycerides.Since the differentiation of preadipocytes and mouse embryonic fibroblasts to adipocytes was markedly facilitated by either pharmacological blockade or genetic deletion/inhibition of EP3 receptor via the cAMP/PKA/PPARγpathway,increased adipogenesis may contribute to obesity in EP3^(−/−)and EP3βmice.Moreover,both EP3^(−/−)and EP3βmice had increased lipolysis in WAT mainly due to the activated cAMP/PKA/hormone-sensitive lipase pathway.Taken together,our findings suggest that EP3 receptor and itsαandγisoforms are involved in both adipogenesis and lipolysis and influence food intake,serum lipid levels,and insulin sensitivity.
