Biological Science Laboratories, Kao Corporation, 2606 Akabane, Ichikai-machi, Haga-gun, Tochigi 321-3497, Japan.
Am J Physiol Endocrinol Metab. 2011 Jan;300(1):E122-33. doi: 10.1152/ajpendo.00441.2010. Epub 2010 Oct 13.
The prevalence of obesity is increasing globally, and obesity is a major risk factor for type 2 diabetes and cardiovascular disease. We investigated the effects of coffee polyphenols (CPP), which are abundant in coffee and consumed worldwide, on diet-induced body fat accumulation. C57BL/6J mice were fed either a control diet, a high-fat diet, or a high-fat diet supplemented with 0.5 to 1.0% CPP for 2-15 wk. Supplementation with CPP significantly reduced body weight gain, abdominal and liver fat accumulation, and infiltration of macrophages into adipose tissues. Energy expenditure evaluated by indirect calorimetry was significantly increased in CPP-fed mice. The mRNA levels of sterol regulatory element-binding protein (SREBP)-1c, acetyl-CoA carboxylase-1 and -2, stearoyl-CoA desaturase-1, and pyruvate dehydrogenase kinase-4 in the liver were significantly lower in CPP-fed mice than in high-fat control mice. Similarly, CPP suppressed the expression of these molecules in Hepa 1-6 cells, concomitant with an increase in microRNA-122. Structure-activity relationship studies of nine quinic acid derivatives isolated from CPP in Hepa 1-6 cells suggested that mono- or di-caffeoyl quinic acids (CQA) are active substances in the beneficial effects of CPP. Furthermore, CPP and 5-CQA decreased the nuclear active form of SREBP-1, acetyl-CoA carboxylase activity, and cellular malonyl-CoA levels. These findings indicate that CPP enhances energy metabolism and reduces lipogenesis by downregulating SREBP-1c and related molecules, which leads to the suppression of body fat accumulation.
肥胖症在全球范围内的患病率不断上升，肥胖是 2 型糖尿病和心血管疾病的主要危险因素。我们研究了咖啡多酚（CPP）的作用，CPP 在咖啡中含量丰富，在全球范围内消费。我们研究了咖啡多酚（CPP）对饮食诱导的体脂肪积累的影响。C57BL/6J 小鼠分别喂食对照饮食、高脂肪饮食或补充 0.5%至 1.0%CPP 的高脂肪饮食 2-15 周。CPP 补充显著降低了体重增加、腹部和肝脏脂肪积累以及巨噬细胞浸润到脂肪组织。通过间接量热法评估的能量消耗在 CPP 喂养的小鼠中显著增加。肝脏中固醇调节元件结合蛋白（SREBP）-1c、乙酰辅酶 A 羧化酶-1 和 -2、硬脂酰辅酶 A 去饱和酶-1 和丙酮酸脱氢酶激酶-4 的 mRNA 水平在 CPP 喂养的小鼠中显著低于高脂肪对照组。同样，CPP 抑制了 Hepa 1-6 细胞中这些分子的表达，同时 microRNA-122 增加。从 CPP 中分离出的 9 种奎宁酸衍生物在 Hepa 1-6 细胞中的结构活性关系研究表明，单或二咖啡酰奎宁酸（CQA）是 CPP 有益作用的活性物质。此外，CPP 和 5-CQA 降低了 SREBP-1 的核活性形式、乙酰辅酶 A 羧化酶活性和细胞丙二酰辅酶 A 水平。这些发现表明，CPP 通过下调 SREBP-1c 和相关分子增强能量代谢并减少脂肪生成，从而抑制体脂肪积累。
