Wu Yue-Yue, Zha Ying, Liu Jun, Wang Fang, Xu Jiong, Chen Zao-Ping, Ding He-Yuan, Sheng Li, Han Xiao-Jie
Department of Endocrinology, Shanghai Fifth People's Hospital Affiliated to Fudan University, Shanghai, 200240, China.
Department of Science and Education, Shanghai Fifth People's Hospital Affiliated to Fudan University, Shanghai, 200240, China.
Chin J Integr Med. 2016 Nov 17. doi: 10.1007/s11655-016-2518-x.
To assess the effects of berberine (BBR) on high-molecular weight (HMW) adiponectin and adiponectin receptors (adipoR1/adipoR2) expressions in high-fat (HF) diet fed rats.
Forty Wistar male rats were randomly assigned into a normal diet fed group and three HF diet (fat for 45% calories) fed groups (n=10 for each group). All rats underwent 12 weeks of feeding. After 4 weeks feeding, rats in the two of three HF diet fed groups were treated with 150 mg·kg·day BBR (HF+LBBR group) and 380 mg·kg·day BBR (HF+HBBR group) by gavage once a day respectively for the next 8 weeks while the rats in other groups treated with vehicle (NF+Veh and HF+Veh). Body weight and food intake were observed and recorded on daily basis. At the end of 12 weeks, the blood, liver, epididymal fat tissues and quadriceps femoris muscles were collected. Fasting insulin, plasma fasting glucose, serum free fatty acid (FFA), total adiponectin and HMW adiponectin levels were measured by enzyme linked immunosorbent assay method. Glucose tolerance test (GTT) and insulin tolerance test (ITT) were performed to determine the insulinsensitizing. Meanwhile the homeostasis model assessment (HOMA) method was used to determine insulin resistance (HOMA-IR). The expressions of adipoR1, adipoR2 and adenosine monophophate activated protein kinase (AMPK) phosphorylation level in skeletal muscle and liver tissue were detected by Western blot. Liver and kidney toxicity were evaluated during treatment.
The body weight of rats in high- or low-dose BBR group reduced as well as HOMA-IR, FFA concentrations and fasting insulin levels decreased compared with HF+Veh group (P<0.05). BBR also increased the ratio of HMW to total adiponectin in high fat-fed rats compared with rats in the HF+Veh group. High- and low-dose BBR increased adipoR1 expression in skeletal muscle by over 6- and 2-fold (P<0.05), respectively, and high-dose BBR also increased adipoR2 expression in liver tissue by over 2-fold (P<0.05). BBR significantly increased AMPK phosphorylation in HF diet rats compared with normal diet rats (P<0.05). The ratio of HMW to total adiponectin was inversely correlated with HOMA-IR (r=-0.52, P=0.001). Meantime, no liver and kidney toxicity was found in high fat-fed rats that treated by BBR.
Berberine may improve insulin resistance by increasing the expression of adiponectin receptors and the ratio of HMW to total adiponectin.
评估小檗碱（BBR）对高脂饮食喂养大鼠高分子量（HMW）脂联素及脂联素受体（adipoR1/adipoR2）表达的影响。
40只雄性Wistar大鼠随机分为正常饮食喂养组和3个高脂饮食（脂肪供能占45%）喂养组（每组n = 10）。所有大鼠均接受12周喂养。喂养4周后，3个高脂饮食喂养组中的2组大鼠分别在接下来的8周内每天经口灌胃给予150 mg·kg·天BBR（HF + LBBR组）和380 mg·kg·天BBR（HF + HBBR组），而其他组大鼠给予溶媒（NF + Veh和HF + Veh）。每天观察并记录体重和食物摄入量。12周结束时，采集血液、肝脏、附睾脂肪组织和股四头肌。采用酶联免疫吸附测定法测量空腹胰岛素、血浆空腹血糖、血清游离脂肪酸（FFA）、总脂联素和HMW脂联素水平。进行葡萄糖耐量试验（GTT）和胰岛素耐量试验（ITT）以确定胰岛素敏感性。同时采用稳态模型评估（HOMA）法确定胰岛素抵抗（HOMA - IR）。通过蛋白质免疫印迹法检测骨骼肌和肝脏组织中adipoR1、adipoR2的表达及腺苷单磷酸活化蛋白激酶（AMPK）的磷酸化水平。治疗期间评估肝脏和肾脏毒性。
与HF + Veh组相比，高、低剂量BBR组大鼠体重降低，HOMA - IR、FFA浓度和空腹胰岛素水平下降（P < 0.05）。与HF + Veh组大鼠相比，BBR还增加了高脂喂养大鼠中HMW脂联素与总脂联素的比例。高、低剂量BBR分别使骨骼肌中adipoR1表达增加6倍和2倍以上（P < 0.05），高剂量BBR还使肝脏组织中adipoR2表达增加2倍以上（P < 0.05）。与正常饮食大鼠相比，BBR显著增加了高脂饮食大鼠中AMPK的磷酸化水平（P < 0.05）。HMW脂联素与总脂联素的比例与HOMA - IR呈负相关（r = - 0.52，P = 0.001）。同时，BBR治疗的高脂喂养大鼠未发现肝脏和肾脏毒性。
小檗碱可能通过增加脂联素受体表达及HMW脂联素与总脂联素的比例来改善胰岛素抵抗。
