Chlorogenic acid improves high fat diet-induced hepatic steatosis and insulin resistance in mice.

Chlorogenic acid improves high fat diet-induced hepatic steatosis and insulin resistance in mice.
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DOI:
10.1007/s11095-014-1526-9
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发表时间:
2015-04
影响因子:
3.7
通讯作者:
Liu D
Liu D
中科院分区:
医学3区
文献类型:
--
作者:
Ma Y;Gao M;Liu D

文献摘要

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绿原酸(Chlorogenic acid,CGA)是咖啡中含量最丰富的成分,具有多种生物活性.本研究的目的是评估CGA对肥胖和肥胖相关的肝脏脂肪变性和胰岛素抵抗的预防和治疗作用。进行了两组实验。在第1组中,6周龄C57 BL/6小鼠喂食常规食物或高脂肪饮食(HFD)15周,每周两次腹膜内(IP)注射CGA(100 mg/kg)或DMSO(载体溶液)。在第2组中,肥胖小鼠(平均50 g)用CGA(100 mg/kg,IP,每周两次)或DMSO处理6周。监测体重、身体组成和摄食量。在研究结束时测量血糖、胰岛素和脂质水平。评价肝脏脂质蓄积和葡萄糖稳态。另外,通过真实的时间PCR分析涉及脂质代谢和炎症的基因。CGA显著阻断饮食诱导的肥胖的发展,但不影响肥胖小鼠的体重。CGA治疗抑制HFD诱导的肝脂肪变性和胰岛素抵抗。定量PCR分析显示CGA处理抑制了肝脏Pparγ、Cd 36、Fabp 4和Mgat 1基因的表达。CGA处理还减弱了肝脏和白色脂肪组织中的炎症,伴随着巨噬细胞标志物基因的mRNA水平的降低,所述巨噬细胞标志物基因包括编码炎性蛋白的F4/80、Cd 68、Cd 11b、Cd 11 c和Tnfa、Mcp-1和Ccr 2。我们的研究提供了直接的证据,支持CGA作为一种有效的化合物,在预防饮食诱导的肥胖和肥胖相关的代谢综合征。我们的研究结果表明,喝咖啡有利于维持高脂肪饮食时的代谢平衡。
Chlorogenic acid (CGA), the most abundant component in coffee, has exhibited many biological activities. The objective of this study is to assess preventive and therapeutic effects of CGA on obesity and obesity-related liver steatosis and insulin resistance. Two sets of experiments were conducted. In set 1, 6-week old C57BL/6 mice were fed a regular chow or high-fat diet (HFD) for 15 weeks with twice intra-peritoneal (IP) injection of CGA (100 mg/kg) or DMSO (carrier solution) per week. In set 2, obese mice (average 50 g) were treated by CGA (100 mg/kg, IP, twice weekly) or DMSO for 6 weeks. Body weight, body composition and food intake were monitored. Blood glucose, insulin and lipid levels were measured at end of the study. Hepatic lipid accumulation and glucose homeostasis were evaluated. Additionally, genes involved in lipid metabolism and inflammation were analyzed by real time PCR. CGA significantly blocked the development of diet-induced obesity but did not affect body weight in obese mice. CGA treatment curbed HFD-induced hepatic steatosis and insulin resistance. Quantitative PCR analysis shows that CGA treatment suppressed hepatic expression Pparγ, Cd36, Fabp4, and Mgat1 gene. CGA treatment also attenuated inflammation in the liver and white adipose tissue accompanied by a decrease in mRNA levels of macrophage marker genes including F4/80, Cd68, Cd11b, Cd11c, and Tnfa, Mcp-1 and Ccr2 encoding inflammatory proteins. Our study provides direct evidence in support of CGA as a potent compound in preventing diet-induced obesity and obesity-related metabolic syndrome. Our results suggest that drinking coffee is beneficial in maintaining metabolic homeostasis when on a high fat diet.