Tain You-Lin, Hsu Chien-Ning, Chan Julie Y H
Departments of Pediatrics, Kaohsiung Chang Gung Memorial Hospital, Chang Gung University College of Medicine, Kaohsiung 833, Taiwan.
Institute for Translational Research in Biomedicine, Kaohsiung Chang Gung Memorial Hospital, Chang Gung University College of Medicine, Kaohsiung 833, Taiwan.
Int J Mol Sci. 2015 Dec 24;17(1):20. doi: 10.3390/ijms17010020.
Hypertension is an important component of metabolic syndrome. Adulthood hypertension and metabolic syndrome can be programmed in response to nutritional insults in early life. Peroxisome proliferator-activated receptors (PPARs) serve as a nutrient-sensing signaling linking nutritional programming to hypertension and metabolic syndrome. All three members of PPARs, PPARα, PPARβ/δ, and PPARγ, are expressed in the kidney and involved in blood pressure control. This review provides an overview of potential clinical applications of targeting on the PPARs in the kidney to prevent programmed hypertension and metabolic syndrome, with an emphasis on the following areas: mechanistic insights to interpret programmed hypertension; the link between the PPARs, nutritional insults, and programmed hypertension and metabolic syndrome; the impact of PPAR signaling pathway in a maternal high-fructose model; and current experimental studies on early intervention by PPAR modulators to prevent programmed hypertension and metabolic syndrome. Animal studies employing a reprogramming strategy via targeting PPARs to prevent hypertension have demonstrated interesting results. It is critical that the observed effects on developmental reprogramming in animal models are replicated in human studies, to halt the globally-growing epidemic of metabolic syndrome-related diseases.
高血压是代谢综合征的一个重要组成部分。成年期高血压和代谢综合征可因早年的营养损伤而被编程。过氧化物酶体增殖物激活受体(PPARs)作为一种营养感应信号,将营养编程与高血压和代谢综合征联系起来。PPARs的所有三个成员,即PPARα、PPARβ/δ和PPARγ,均在肾脏中表达,并参与血压调控。本综述概述了靶向肾脏中的PPARs以预防编程性高血压和代谢综合征的潜在临床应用,重点关注以下方面:解释编程性高血压的机制见解;PPARs、营养损伤与编程性高血压和代谢综合征之间的联系;PPAR信号通路在母体高果糖模型中的影响;以及目前关于PPAR调节剂早期干预以预防编程性高血压和代谢综合征的实验研究。采用通过靶向PPARs预防高血压的重编程策略的动物研究已取得了有趣的结果。至关重要的是,在动物模型中观察到的对发育重编程的影响要在人体研究中得到重现,以遏制全球范围内与代谢综合征相关疾病的流行趋势。