在动物脂肪沉积过程中,前体脂肪细胞增殖、分化和脂滴甘油三酯水平的变化受到一系列转录因子和信号通路的调节。目前研究者虽对脂肪形成的转录调控机制进行了深入研究,但对转录后mRNA水平修饰的报道相对较少。甲基化转移酶、去甲基化酶...在动物脂肪沉积过程中,前体脂肪细胞增殖、分化和脂滴甘油三酯水平的变化受到一系列转录因子和信号通路的调节。目前研究者虽对脂肪形成的转录调控机制进行了深入研究,但对转录后mRNA水平修饰的报道相对较少。甲基化转移酶、去甲基化酶和甲基化阅读蛋白共同调控的mRNA m^(6)A修饰是动态可逆的且与脂肪沉积密切相关。脂肪含量和肥胖相关蛋白(fat mass and obesityassociated,FTO)作为RNA去甲基化酶,影响被修饰基因的表达,在脂肪沉积中起关键作用。文中系统分析并总结了FTO介导的mRNA m^(6)A去甲基化对动物脂肪沉积的作用及分子调控机制的研究进展,提示FTO可能成为有效治疗肥胖症的靶点;还对近年来研发FTO抑制剂的情况进行了总结,并展望其在治疗肥胖症方面的研究前景。展开更多
Obesity is usually considered as an overweight or excess body fat, leading to increased health problems. Obesity is a major risk factor for a number of serious diseases. Decreasing dietary fat absorption, through inhi...Obesity is usually considered as an overweight or excess body fat, leading to increased health problems. Obesity is a major risk factor for a number of serious diseases. Decreasing dietary fat absorption, through inhibition of pancreatic lipase activity, has been reported to be one of the most effective ways for managing obesity. The present study was aimed at investigating lipase inhibitors from edible plants. A lipase inhibitor was isolated from n-hexane and ethyl acetate extracts of the ripe fruits of Solanum stramonifolium Jacq. by column chromatography and identified by spectral analysis. Its structure was elucidated as (22R)-3β-benzoyloxy-22-hydroxy-4α-methyl-5α-stigmast-7-en-6-one or carpesterol (1). Carpesterol exhibited moderate lipase inhibition activity with IC50 value of 56.0 μg/mL while orlistat, a well- know pancreatic lipase inhibitor, had IC50 value of 3.5 ng/mL. Moreover, the kinetic properties of carpesterol on pancreatic lipase were evaluated. Carpesterol is a competitive inhibitor and exhibited antagonistic interaction when combined with orlistat on lipase inhibition activity.展开更多
Obesity is increasingly prevalent globally, searching for therapeutic agents acting on adipose tissue is of great importance. Equisetin(EQST), a meroterpenoid isolated from a marine sponge-derived fungus, has been rep...Obesity is increasingly prevalent globally, searching for therapeutic agents acting on adipose tissue is of great importance. Equisetin(EQST), a meroterpenoid isolated from a marine sponge-derived fungus, has been reported to display antibacterial and antiviral activities. Here, we revealed that EQST displayed anti-obesity effects acting on adipose tissue through inhibiting adipogenesis in vitro and attenuating HFD-induced obesity in mice, doing so without affecting food intake, blood pressure or heart rate.We demonstrated that EQST inhibited the enzyme activity of 11β-hydroxysteroid dehydrogenase type 1(11β-HSD1), a therapeutic target of obesity in adipose tissue. Anti-obesity properties of EQST were all offset by applying excessive 11β-HSD1’s substrates and 11β-HSD1 inhibition through knockdown in vitro or 11β-HSD1 knockout in vivo. In the 11β-HSD1 bypass model constructed by adding excess11β-HSD1 products, EQST’s anti-obesity effects disappeared. Furthermore, EQST directly bond to11β-HSD1 protein and presented remarkable better intensity on 11β-HSD1 inhibition and better efficacy on anti-obesity than known 11β-HSD1 inhibitor. Therefore, EQST can be developed into anti-obesity candidate compound, and this study may provide more clues for developing higher effective 11β-HSD1 inhibitors.展开更多
目的探讨幼年肥胖Sprague-Dawlely(SD)大鼠脂肪组织vaspin含量与胰岛素敏感性的关系。方法断乳3周SD大鼠24只,随机分为高脂饮食组和普通饮食组,每组12只。成功建模后,测定各组体重、腹围。禁食12 h后取内眦静脉血测定空腹血糖(FPG)、空...目的探讨幼年肥胖Sprague-Dawlely(SD)大鼠脂肪组织vaspin含量与胰岛素敏感性的关系。方法断乳3周SD大鼠24只,随机分为高脂饮食组和普通饮食组,每组12只。成功建模后,测定各组体重、腹围。禁食12 h后取内眦静脉血测定空腹血糖(FPG)、空腹胰岛素(FINS);再腹腔注射50%葡萄糖(2 g/kg),于注射后60 min、120 min再次取内眦静脉血测定各时间点血糖(BG)及胰岛素(INS)。幼鼠处死后将内脏脂肪组织称重。酶联免疫吸附法测定各组幼鼠内脏脂肪组织中vaspin的含量,并对vaspin表达量与各体格测量指标及胰岛素敏感性评价指标进行相关性分析。结果高脂饮食组大鼠的体重、腹围、内脏脂肪重量、FPG、FINS、120 min INS、vaspin、胰岛素抵抗指数(HOMA-IR)、胰岛素分泌指数(HOMA-β)均高于普通饮食组(P<0.05),高脂饮食组胰岛素敏感指数(ISI)明显低于普通饮食组(P<0.01)。Vaspin含量与肝脏重量、内脏脂肪重量、腹围、120 min INS、FPG、FINS、HOMA-IR、HOMA-β呈正相关(P<0.05),而与ISI呈负相关(P<0.05)。结论幼年肥胖SD大鼠胰岛素抵抗状态与vaspin高水平表达有关,推测vaspin是一种增加胰岛素敏感性、促进胰岛β细胞分泌胰岛素和改善糖耐量的脂肪细胞因子,可能参与了胰岛素抵抗、糖代谢紊乱状态的形成。展开更多
文摘在动物脂肪沉积过程中,前体脂肪细胞增殖、分化和脂滴甘油三酯水平的变化受到一系列转录因子和信号通路的调节。目前研究者虽对脂肪形成的转录调控机制进行了深入研究,但对转录后mRNA水平修饰的报道相对较少。甲基化转移酶、去甲基化酶和甲基化阅读蛋白共同调控的mRNA m^(6)A修饰是动态可逆的且与脂肪沉积密切相关。脂肪含量和肥胖相关蛋白(fat mass and obesityassociated,FTO)作为RNA去甲基化酶,影响被修饰基因的表达,在脂肪沉积中起关键作用。文中系统分析并总结了FTO介导的mRNA m^(6)A去甲基化对动物脂肪沉积的作用及分子调控机制的研究进展,提示FTO可能成为有效治疗肥胖症的靶点;还对近年来研发FTO抑制剂的情况进行了总结,并展望其在治疗肥胖症方面的研究前景。
文摘Obesity is usually considered as an overweight or excess body fat, leading to increased health problems. Obesity is a major risk factor for a number of serious diseases. Decreasing dietary fat absorption, through inhibition of pancreatic lipase activity, has been reported to be one of the most effective ways for managing obesity. The present study was aimed at investigating lipase inhibitors from edible plants. A lipase inhibitor was isolated from n-hexane and ethyl acetate extracts of the ripe fruits of Solanum stramonifolium Jacq. by column chromatography and identified by spectral analysis. Its structure was elucidated as (22R)-3β-benzoyloxy-22-hydroxy-4α-methyl-5α-stigmast-7-en-6-one or carpesterol (1). Carpesterol exhibited moderate lipase inhibition activity with IC50 value of 56.0 μg/mL while orlistat, a well- know pancreatic lipase inhibitor, had IC50 value of 3.5 ng/mL. Moreover, the kinetic properties of carpesterol on pancreatic lipase were evaluated. Carpesterol is a competitive inhibitor and exhibited antagonistic interaction when combined with orlistat on lipase inhibition activity.
基金supported by the following grants:CXYJ-2021-04 from the Research Foundation of Capital Institute of Pediatrics(China)81573436 from National Natural Science Foundation of China2018ZX09711-001-001-016 from the Found of the National New Drug Innovation Major Project of China。
文摘Obesity is increasingly prevalent globally, searching for therapeutic agents acting on adipose tissue is of great importance. Equisetin(EQST), a meroterpenoid isolated from a marine sponge-derived fungus, has been reported to display antibacterial and antiviral activities. Here, we revealed that EQST displayed anti-obesity effects acting on adipose tissue through inhibiting adipogenesis in vitro and attenuating HFD-induced obesity in mice, doing so without affecting food intake, blood pressure or heart rate.We demonstrated that EQST inhibited the enzyme activity of 11β-hydroxysteroid dehydrogenase type 1(11β-HSD1), a therapeutic target of obesity in adipose tissue. Anti-obesity properties of EQST were all offset by applying excessive 11β-HSD1’s substrates and 11β-HSD1 inhibition through knockdown in vitro or 11β-HSD1 knockout in vivo. In the 11β-HSD1 bypass model constructed by adding excess11β-HSD1 products, EQST’s anti-obesity effects disappeared. Furthermore, EQST directly bond to11β-HSD1 protein and presented remarkable better intensity on 11β-HSD1 inhibition and better efficacy on anti-obesity than known 11β-HSD1 inhibitor. Therefore, EQST can be developed into anti-obesity candidate compound, and this study may provide more clues for developing higher effective 11β-HSD1 inhibitors.
文摘目的探讨幼年肥胖Sprague-Dawlely(SD)大鼠脂肪组织vaspin含量与胰岛素敏感性的关系。方法断乳3周SD大鼠24只,随机分为高脂饮食组和普通饮食组,每组12只。成功建模后,测定各组体重、腹围。禁食12 h后取内眦静脉血测定空腹血糖(FPG)、空腹胰岛素(FINS);再腹腔注射50%葡萄糖(2 g/kg),于注射后60 min、120 min再次取内眦静脉血测定各时间点血糖(BG)及胰岛素(INS)。幼鼠处死后将内脏脂肪组织称重。酶联免疫吸附法测定各组幼鼠内脏脂肪组织中vaspin的含量,并对vaspin表达量与各体格测量指标及胰岛素敏感性评价指标进行相关性分析。结果高脂饮食组大鼠的体重、腹围、内脏脂肪重量、FPG、FINS、120 min INS、vaspin、胰岛素抵抗指数(HOMA-IR)、胰岛素分泌指数(HOMA-β)均高于普通饮食组(P<0.05),高脂饮食组胰岛素敏感指数(ISI)明显低于普通饮食组(P<0.01)。Vaspin含量与肝脏重量、内脏脂肪重量、腹围、120 min INS、FPG、FINS、HOMA-IR、HOMA-β呈正相关(P<0.05),而与ISI呈负相关(P<0.05)。结论幼年肥胖SD大鼠胰岛素抵抗状态与vaspin高水平表达有关,推测vaspin是一种增加胰岛素敏感性、促进胰岛β细胞分泌胰岛素和改善糖耐量的脂肪细胞因子,可能参与了胰岛素抵抗、糖代谢紊乱状态的形成。
