Lysophosphatidic acid receptor mRNA levels in heart and white adipose tissue are associated with obesity in mice and humans

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 recep...

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Veröffentlicht in:PloS one 2017-12, Vol.12 (12), p.e0189402-e0189402
Hauptverfasser: 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
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container_issue 12
container_start_page e0189402
container_title PloS one
container_volume 12
creator 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
description 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.
doi_str_mv 10.1371/journal.pone.0189402
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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.</description><identifier>ISSN: 1932-6203</identifier><identifier>EISSN: 1932-6203</identifier><identifier>DOI: 10.1371/journal.pone.0189402</identifier><identifier>PMID: 29236751</identifier><language>eng</language><publisher>United States: Public Library of Science</publisher><subject>Acids ; Adipocytes ; Adipose tissue ; Animal tissues ; Biochemistry ; Biology and Life Sciences ; Body fat ; Cardiomyocytes ; Correlation analysis ; Diagnosis ; Disease ; Gene expression ; Genetic aspects ; Glucose ; Heart ; Heart attacks ; Heart diseases ; Heart failure ; Heart surgery ; Homeostasis ; Hospitals ; Inflammation ; Insulin ; Insulin resistance ; Lipids ; Liver cancer ; Lysophosphatidic acid ; Measurement ; Medicine ; Medicine and Health Sciences ; Messenger RNA ; Metabolic disorders ; Mice ; Mimicry ; Molecular biology ; Myocardium ; Obesity ; Palmitic acid ; Patients ; Physiological aspects ; Receptors ; Risk factors ; Rodents ; Signaling ; Studies ; Sucrose ; Sugar ; Surgery</subject><ispartof>PloS one, 2017-12, Vol.12 (12), p.e0189402-e0189402</ispartof><rights>COPYRIGHT 2017 Public Library of Science</rights><rights>2017 Brown et al. 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Ansar</au><au>Pulinilkunnil, Thomas</au><au>Kienesberger, Petra C</au><au>Souza-Mello, Vanessa</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Lysophosphatidic acid receptor mRNA levels in heart and white adipose tissue are associated with obesity in mice and humans</atitle><jtitle>PloS one</jtitle><addtitle>PLoS One</addtitle><date>2017-12-13</date><risdate>2017</risdate><volume>12</volume><issue>12</issue><spage>e0189402</spage><epage>e0189402</epage><pages>e0189402-e0189402</pages><issn>1932-6203</issn><eissn>1932-6203</eissn><abstract>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.</abstract><cop>United States</cop><pub>Public Library of Science</pub><pmid>29236751</pmid><doi>10.1371/journal.pone.0189402</doi><tpages>e0189402</tpages><orcidid>https://orcid.org/0000-0001-9643-8338</orcidid><oa>free_for_read</oa></addata></record>
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subjects Acids
Adipocytes
Adipose tissue
Animal tissues
Biochemistry
Biology and Life Sciences
Body fat
Cardiomyocytes
Correlation analysis
Diagnosis
Disease
Gene expression
Genetic aspects
Glucose
Heart
Heart attacks
Heart diseases
Heart failure
Heart surgery
Homeostasis
Hospitals
Inflammation
Insulin
Insulin resistance
Lipids
Liver cancer
Lysophosphatidic acid
Measurement
Medicine
Medicine and Health Sciences
Messenger RNA
Metabolic disorders
Mice
Mimicry
Molecular biology
Myocardium
Obesity
Palmitic acid
Patients
Physiological aspects
Receptors
Risk factors
Rodents
Signaling
Studies
Sucrose
Sugar
Surgery
title Lysophosphatidic acid receptor mRNA levels in heart and white adipose tissue are associated with obesity in mice and humans
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