Post-Graduate School, Fujian University of Traditional Chinese Medicine, Fuzhou, China.
Chin J Integr Med. 2012 Apr;18(4):262-8. doi: 10.1007/s11655-012-1023-0. Epub 2012 Mar 30.
To investigate the therapeutic effects of Ping-tang Recipe (, PTR) on high-fat diet (HFD)-induced insulin resistance and non-alcoholic fatty liver disease (NAFLD), and to elucidate the underlying mechanisms.
Forty male SD rats were included in the study. Ten rats were fed on normal diet as normal control, and thirty rats were fed on HFD for 8 weeks to induce obesity, followed with low dose (0.42 g/kg) or high dose (0.84 g/kg) of PTR or vehicle for 8 weeks with 10 animals for each group. Glucose metabolism and insulin sensitivity were evaluated by oral glucose tolerance test and insulin tolerance test. Hepatic steatosis was measured by immunohistochemistry. Liver lipid metabolic genes were analyzed by quantitative real-time polymerase chain reaction, while AMP-activated protein kinase (AMPK) expression was examined by Western blot.
Rats fed on HFD developed abdominal obesity, insulin resistance and NAFLD. PTR treatment reduced visceral fat (peri-epididymal and peri-renal) accumulation, improved glucose metabolism, and attenuated hepatic steatosis. The expressions of the key lipolytic regulating genes, including peroxisome proliferators-activated receptor γ co-activator 1α (PGC-1α), peroxisome proliferator-activated receptor γ (PRAR-γ) and α (PRAR-α), were up-regulated (P<0.05 or P<0.01), while the expressions of lipogenic genes such as sterol regulatory element-binding protein 1c (SREBP-1c), fatty acid synthase (FAS) and liver fatty acid-binding protein (L-FABP) were down-regulated (P<0.05 or P<0.01). In addition, PTR activated AMPK and promoted acetyl-CoA carboxylase phosphorylation in the liver.
PTR improves insulin resistance and reverse hepatic steatosis in the rat model of HFD-induced obesity through promotion of lipolysis and reduction of lipogenesis, which involves the AMPK signaling pathway, thus representing a new therapeutic intervention for obesity related insulin resistance and NAFLD.
探讨平糖方(PTR)对高脂饮食(HFD)诱导的胰岛素抵抗和非酒精性脂肪性肝病(NAFLD)的治疗作用,并阐明其作用机制。
本研究纳入 40 只雄性 SD 大鼠。其中 10 只大鼠给予普通饮食作为正常对照,30 只大鼠给予 HFD 喂养 8 周以诱导肥胖,随后给予低剂量(0.42 g/kg)或高剂量(0.84 g/kg)PTR 或载体 8 周,每组 10 只。通过口服葡萄糖耐量试验和胰岛素耐量试验评估葡萄糖代谢和胰岛素敏感性。通过免疫组织化学法测定肝脂肪变性。采用实时定量聚合酶链反应分析肝脂质代谢基因,Western blot 检测 AMP 激活蛋白激酶(AMPK)的表达。
给予 HFD 的大鼠出现腹部肥胖、胰岛素抵抗和 NAFLD。PTR 治疗可减少内脏脂肪(附睾周和肾周)堆积,改善葡萄糖代谢,并减轻肝脂肪变性。关键脂肪分解调节基因的表达上调,包括过氧化物酶体增殖物激活受体 γ 共激活因子 1α(PGC-1α)、过氧化物酶体增殖物激活受体 γ(PRAR-γ)和 α(PRAR-α)(P<0.05 或 P<0.01),而脂生成基因如固醇调节元件结合蛋白 1c(SREBP-1c)、脂肪酸合成酶(FAS)和肝脂肪酸结合蛋白(L-FABP)的表达下调(P<0.05 或 P<0.01)。此外,PTR 激活 AMPK 并促进肝脏乙酰辅酶 A 羧化酶磷酸化。
PTR 通过促进脂肪分解和减少脂肪生成改善 HFD 诱导肥胖大鼠的胰岛素抵抗和逆转肝脂肪变性,涉及 AMPK 信号通路,因此为肥胖相关胰岛素抵抗和 NAFLD 提供了一种新的治疗干预措施。