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中国精品科技期刊2020
隋怡,鹿田,滕明刚,等. 基于肝脏瘦素抵抗通路探讨刺梨醇提物对食源性肥胖大鼠的降脂作用[J]. 食品工业科技,2025,46(12):389−395. doi: 10.13386/j.issn1002-0306.2024090023.
引用本文: 隋怡,鹿田,滕明刚,等. 基于肝脏瘦素抵抗通路探讨刺梨醇提物对食源性肥胖大鼠的降脂作用[J]. 食品工业科技,2025,46(12):389−395. doi: 10.13386/j.issn1002-0306.2024090023.
SUI Yi, LU Tian, TENG Minggang, et al. Exploring the Lipid-lowering Effects of Rosa roxburghii Tratt. Alcohol Extract on Diet-induced Obesity Rats through Hepatic Leptin Resistance Pathway[J]. Science and Technology of Food Industry, 2025, 46(12): 389−395. (in Chinese with English abstract). doi: 10.13386/j.issn1002-0306.2024090023.
Citation: SUI Yi, LU Tian, TENG Minggang, et al. Exploring the Lipid-lowering Effects of Rosa roxburghii Tratt. Alcohol Extract on Diet-induced Obesity Rats through Hepatic Leptin Resistance Pathway[J]. Science and Technology of Food Industry, 2025, 46(12): 389−395. (in Chinese with English abstract). doi: 10.13386/j.issn1002-0306.2024090023.

基于肝脏瘦素抵抗通路探讨刺梨醇提物对食源性肥胖大鼠的降脂作用

Exploring the Lipid-lowering Effects of Rosa roxburghii Tratt. Alcohol Extract on Diet-induced Obesity Rats through Hepatic Leptin Resistance Pathway

  • 摘要: 目的:探究不同剂量刺梨醇提物对食源性肥胖(diet-induced obesity,DIO)大鼠的降脂作用,并探究其对肝脏瘦素信号通路的影响。方法:SD大鼠随机分为正常组、食源性肥胖(DIO)模型组、刺梨醇提物低(1.25 g/kg)、中(2.5 g/kg)、高(5 g/kg)剂量组。每日给予大鼠高脂饲料造成食源性肥胖模型,以体质量显著升高为造模成功标志。连续造模与给药8周。每日检测大鼠体质量,计算各组大鼠Lee’s指数。末次给药后处死各组大鼠,取血清、肝、脂肪组织。ELISA法检测各组大鼠血清甘油三酯(triglyceride,TG)、总胆固醇(total cholesterol,TC)、低密度脂蛋白(low-density lipoprotein cholesterol,LDL-C)、高密度脂蛋白(high-density lipoprotein cholesterol,HDL-C)含量以及血清瘦素(Leptin)、可溶性瘦素受体(soluble leptin receptor,sLR)含量;HE染色法观察各组大鼠脂肪细胞体积;Western blot法检测各组大鼠肝组织瘦素受体(leptin receptor,LEPR)、蛋白酪氨酸磷酸酶 1B(protein tyrosine phosphatase 1B,PTP1B/PTPN1)、细胞因子信号转导抑制因子3(suppressor of cytokine signaling 3,SOCS3)、信号传导和转录激活因子3(signal transducer and activator of transcription 3,STAT3)、磷酸化STAT3(p-STAT3)蛋白的表达。结果:不同剂量刺梨醇提物于给药后5周显著降低模型组大鼠体质量(P<0.05);给药8周显著降低肥胖大鼠Lee’s指数、血清血脂和瘦素水平(P<0.05),中、高剂量组接近于正常,且能显著升高血清sLR(P<0.05)、显著降低肥胖大鼠白色脂肪组织的脂肪细胞体积(P<0.05)。Western blot结果显示,刺梨醇提物能极显著升高肥胖大鼠肝脏LEPRb蛋白的表达(P<0.01),极显著降低PTP1B、SOCS3蛋白的表达(P<0.01),极显著升高p-STAT3/STAT3比值(P<0.01),且呈现剂量依赖性。结论:刺梨醇提物能显著降低DIO大鼠体质量、Lee’s指数和血脂含量,这一变化与上调肝脏LEPR蛋白表达,下调肝脏瘦素信号通路抑制因子PTP1B、SOCS3蛋白的表达,从而恢复肝脏瘦素信号通路敏感性有关。

     

    Abstract: Objective: To investigate the dose-dependent lipid-lowering effects of Rosa roxburghii Tratt. alcohol extract in diet-induced obese (DIO) rats and examine its regulatory mechanisms through the hepatic leptin signaling pathway. Methods: SD rats were randomly divided into a normal group, a diet-induced obesity model group, and a low- (1.25 g/kg), medium- (2.5 g/kg), and high-dose (5 g/kg) ethanol extracts group. Rats were given high-fat diet every day to create a DIO model, and a significant increase in body weight was used as a sign of successful modeling. Modeling and administration were continued for 8 weeks. The body weight of rats was measured daily, and the Lee's index of rats in each group was calculated. After the final dose administration, all rats in each group were euthanized, and their serum, liver, and adipose tissues were collected. The ELISA method was used to detect serum triglyceride (TG), total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein (HDL-C), leptin (Leptin) and soluble leptin receptor (sLR) content of rats in each group. HE staining was employed to measure adipocyte cross-sectional areas in rat tissues across experimental groups. Western blot analysis quantified the protein expression levels of leptin receptor (LEPR), protein tyrosine phosphatase 1B (PTP1B/PTPN1), suppressor of cytokine signaling 3 (SOCS3), and both total and phosphorylated STAT3 (p-STAT3) in hepatic tissues from each group. Results: Different doses of Rosa roxburghii Tratt. alcohol extract significantly decreased body weight in model group rats at 5 weeks post-administration (P<0.05). By week 8, the treatment significantly lowered Lee's index, serum lipid profiles, and leptin levels in obese rats (P<0.05), with medium- and high-dose groups approaching levels observed in the normal control group. Additionally, the extract significantly elevated serum soluble leptin receptor (sLR) levels (P<0.05) and reduced white adipose tissue adipocyte cross-sectional areas (P<0.05). Western blot analysis revealed dose-dependent effects. The extract upregulated hepatic leptin receptor (LEPRb) protein expression (P<0.01), downregulated protein tyrosine phosphatase 1B (PTP1B) and suppressor of cytokine signaling 3 (SOCS3) levels (P<0.01), while enhancing phosphorylated STAT3 (p-STAT3) to total STAT3 ratios (P<0.01). Conclusion: Rosa roxburghii Tratt. alcohol extract significantly reduced body weight, Lee's index, and serum lipid levels in diet-induced obese (DIO) rats. These metabolic improvements were mediated by upregulating hepatic leptin receptor (LEPR) expression and downregulating key inhibitory factors of the leptin signaling pathway (protein tyrosine phosphatase 1B (PTP1B) and suppressor of cytokine signaling 3 (SOCS3)), thereby restoring leptin pathway sensitivity in the liver.

     

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