Brown Amy, Hossain Intekhab, Perez Lester J, Nzirorera Carine, Tozer Kathleen, D'Souza Kenneth, Trivedi Purvi C, Aguiar Christie, Yip Alexandra M, Shea Jennifer, Brunt Keith R, Legare Jean-Francois, Hassan Ansar, Pulinilkunnil Thomas, Kienesberger Petra C
Department of Biochemistry and Molecular Biology, Faculty of Medicine, Dalhousie University, Dalhousie Medicine New Brunswick, Saint John, New Brunswick, Canada.
Cardiovascular Research New Brunswick, Saint John Regional Hospital, Saint John, New Brunswick, Canada.
PLoS One. 2017 Dec 13;12(12):e0189402. doi: 10.1371/journal.pone.0189402. eCollection 2017.
Lysophosphatidic acid (LPA) receptor signaling has been implicated in cardiovascular and obesity-related metabolic disease. However, the distribution and regulation of LPA receptors in the myocardium and adipose tissue remain unclear.
This study aimed to characterize the mRNA expression of LPA receptors (LPA1-6) in the murine and human myocardium and adipose tissue, and its regulation in response to obesity.
LPA receptor mRNA levels were determined by qPCR in i) heart ventricles, isolated cardiomyocytes, and perigonadal adipose tissue from chow or high fat-high sucrose (HFHS)-fed male C57BL/6 mice, ii) 3T3-L1 adipocytes and HL-1 cardiomyocytes under conditions mimicking gluco/lipotoxicity, and iii) human atrial and subcutaneous adipose tissue from non-obese, pre-obese, and obese cardiac surgery patients.
LPA1-6 were expressed in myocardium and white adipose tissue from mice and humans, except for LPA3, which was undetectable in murine adipocytes and human adipose tissue. Obesity was associated with increased LPA4, LPA5 and/or LPA6 levels in mice ventricles and cardiomyocytes, HL-1 cells exposed to high palmitate, and human atrial tissue. LPA4 and LPA5 mRNA levels in human atrial tissue correlated with measures of obesity. LPA5 mRNA levels were increased in HFHS-fed mice and insulin resistant adipocytes, yet were reduced in adipose tissue from obese patients. LPA4, LPA5, and LPA6 mRNA levels in human adipose tissue were negatively associated with measures of obesity and cardiac surgery outcomes. This study suggests that obesity leads to marked changes in LPA receptor expression in the murine and human heart and white adipose tissue that may alter LPA receptor signaling during obesity.
溶血磷脂酸（LPA）受体信号传导与心血管疾病及肥胖相关代谢疾病有关。然而，LPA受体在心肌和脂肪组织中的分布及调控仍不清楚。
本研究旨在描述LPA受体（LPA1 - 6）在小鼠和人类心肌及脂肪组织中的mRNA表达情况，以及其对肥胖的反应调控。
通过定量聚合酶链反应（qPCR）测定LPA受体mRNA水平，样本包括：i）用普通饲料或高脂高蔗糖（HFHS）喂养的雄性C57BL/6小鼠的心室、分离的心肌细胞和性腺周围脂肪组织；ii）在模拟糖/脂毒性条件下的3T3 - L1脂肪细胞和HL - 1心肌细胞；iii）来自非肥胖、肥胖前期和肥胖心脏手术患者的人类心房和皮下脂肪组织。
LPA1 - 6在小鼠和人类的心肌及白色脂肪组织中均有表达，但LPA3在小鼠脂肪细胞和人类脂肪组织中未检测到。肥胖与小鼠心室和心肌细胞、暴露于高棕榈酸的HL - 1细胞以及人类心房组织中LPA4、LPA5和/或LPA6水平升高有关。人类心房组织中LPA４和LPA5的mRNA水平与肥胖指标相关。HFHS喂养的小鼠和胰岛素抵抗脂肪细胞中LPA5的mRNA水平升高，但肥胖患者脂肪组织中该水平降低。人类脂肪组织中LPA4、LPA5和LPA6的mRNA水平与肥胖指标及心脏手术结果呈负相关。本研究表明，肥胖导致小鼠和人类心脏及白色脂肪组织中LPA受体表达发生显著变化，这可能在肥胖过程中改变LPA受体信号传导。
