TY - JOUR
T1 - Lysophosphatidic acid receptor mRNA levels in heart and white adipose tissue are associated with obesity in mice and humans
AU - Brown, Amy
AU - Hossain, Intekhab
AU - Perez, Lester J.
AU - Nzirorera, Carine
AU - Tozer, Kathleen
AU - D’Souza, Kenneth
AU - Trivedi, Purvi C.
AU - Aguiar, Christie
AU - Yip, Alexandra M.
AU - Shea, Jennifer
AU - Brunt, Keith R.
AU - Legare, Jean Francois
AU - Hassan, Ansar
AU - Pulinilkunnil, Thomas
AU - Kienesberger, Petra C.
N1 - This work was supported by a Natural Sciences and Engineering Research Council of Canada (http://www.nserc-crsng.gc.ca/index_eng. asp) Discovery Grant (RGPIN-2014-04454), and grants from the Banting Research Foundation (http://bantingresearchfoundation.ca), the New Brunswick Health Research Foundation (https:// www.nbhrf.com), the New Brunswick Innovation Foundation (http://nbif.ca/en/about_nbif/), and We would like to thank the IMPART team (impart.team) for assistance with the clinical arm of the study.
PY - 2017/12
Y1 - 2017/12
N2 - Background 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. Objectives 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. Methods 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. Results 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.
AB - Background 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. Objectives 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. Methods 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. Results 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.
UR - https://www.scopus.com/pages/publications/85038262247
UR - https://www.scopus.com/pages/publications/85038262247#tab=citedBy
U2 - 10.1371/journal.pone.0189402
DO - 10.1371/journal.pone.0189402
M3 - Article
C2 - 29236751
AN - SCOPUS:85038262247
SN - 1932-6203
VL - 12
JO - PloS one
JF - PloS one
IS - 12
M1 - e0189402
ER -