Hara Takafumi, Kashihara Daiji, Ichimura Atsuhiko, Kimura Ikuo, Tsujimoto Gozoh, Hirasawa Akira
Department of Pharmacogenomics, Graduate School of Pharmaceutical Sciences, Kyoto University, 46-29 Yoshida-Shimoadachi-cho, Sakyo-ku, Kyoto 606-8501, Japan.
Department of Pharmacogenomics, Graduate School of Pharmaceutical Sciences, Kyoto University, 46-29 Yoshida-Shimoadachi-cho, Sakyo-ku, Kyoto 606-8501, Japan.
Biochim Biophys Acta. 2014 Sep;1841(9):1292-300. doi: 10.1016/j.bbalip.2014.06.002. Epub 2014 Jun 10.
Free fatty acids (FFAs) are energy-generating nutrients that act as signaling molecules in various cellular processes. Several orphan G protein-coupled receptors (GPCRs) that act as FFA receptors (FFARs) have been identified and play important physiological roles in various diseases. FFA ligands are obtained from food sources and metabolites produced during digestion and lipase degradation of triglyceride stores. FFARs can be grouped according to ligand profiles, depending on the length of carbon chains of the FFAs. Medium- and long-chain FFAs activate FFA1/GPR40 and FFA4/GPR120. Short-chain FFAs activate FFA2/GPR43 and FFA3/GPR41. However, only medium-chain FFAs, and not long-chain FFAs, activate GPR84 receptor. A number of pharmacological and physiological studies have shown that these receptors are expressed in various tissues and are primarily involved in energy metabolism. Because an impairment of these processes is a part of the pathology of obesity and type 2 diabetes, FFARs are considered as key therapeutic targets. Here, we reviewed recently published studies on the physiological functions of these receptors, primarily focusing on energy homeostasis.
游离脂肪酸（FFAs）是产生能量的营养素，在各种细胞过程中充当信号分子。已鉴定出几种作为游离脂肪酸受体（FFARs）的孤儿G蛋白偶联受体（GPCRs），它们在各种疾病中发挥重要的生理作用。FFA配体来源于食物来源以及甘油三酯储存的消化和脂肪酶降解过程中产生的代谢产物。FFARs可根据配体谱进行分组，这取决于FFAs的碳链长度。中链和长链FFAs激活FFA1/GPR40和FFA4/GPR120。短链FFAs激活FFA2/GPR43和FFA3/GPR41。然而，只有中链FFAs，而不是长链FFAs，能激活GPR84受体。大量的药理学和生理学研究表明，这些受体在各种组织中表达，主要参与能量代谢。由于这些过程的受损是肥胖症和2型糖尿病病理学的一部分，FFARs被视为关键的治疗靶点。在此，我们综述了最近发表的关于这些受体生理功能的研究，主要关注能量稳态。
