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Cholesterol efflux from macrophages is influenced differentially by plasmas from overweight insulin-sensitive and -resistant subjects

Objective: In vitro measurements of cholesterol efflux from macrophages have recently been shown to associate with cardiovascular risk. We investigated whether cholesterol efflux from macrophages incubated with plasmas from overweight/obese subjects with metabolic syndrome was influenced by the pres...

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Published in:International Journal of Obesity 2012-03, Vol.36 (3), p.407-413
Main Authors: Nestel, P, Hoang, A, Sviridov, D, Straznicky, N
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container_title International Journal of Obesity
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description Objective: In vitro measurements of cholesterol efflux from macrophages have recently been shown to associate with cardiovascular risk. We investigated whether cholesterol efflux from macrophages incubated with plasmas from overweight/obese subjects with metabolic syndrome was influenced by the presence of insulin resistance. Methods: Plasmas were obtained from 47 men and women with metabolic syndrome, of whom 25 were found to be insulin resistant (IR) and 22 insulin sensitive (IS) (Matsuda, De Fronzo equation based on oral glucose tolerance test). Activated human macrophage THP-1 cells in which cholesterol had been radiolabelled were incubated with the subjects’ plasmas to allow calculation of % cholesterol efflux. Results: Body mass index and waist measurements, as well as plasma lipid levels, did not differ between the two groups. Homeostatic model assessment-insulin resistance value as well as plasma insulin and leptin concentrations were higher in IR subjects. Cholesterol efflux was found to be significantly greater with plasmas from IR subjects (9.1%) than from IS subjects (6.7%) ( P =0.005). Further, cholesterol efflux was significantly inversely associated with insulin sensitivity index ( P
doi_str_mv 10.1038/ijo.2011.170
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We investigated whether cholesterol efflux from macrophages incubated with plasmas from overweight/obese subjects with metabolic syndrome was influenced by the presence of insulin resistance. Methods: Plasmas were obtained from 47 men and women with metabolic syndrome, of whom 25 were found to be insulin resistant (IR) and 22 insulin sensitive (IS) (Matsuda, De Fronzo equation based on oral glucose tolerance test). Activated human macrophage THP-1 cells in which cholesterol had been radiolabelled were incubated with the subjects’ plasmas to allow calculation of % cholesterol efflux. Results: Body mass index and waist measurements, as well as plasma lipid levels, did not differ between the two groups. Homeostatic model assessment-insulin resistance value as well as plasma insulin and leptin concentrations were higher in IR subjects. Cholesterol efflux was found to be significantly greater with plasmas from IR subjects (9.1%) than from IS subjects (6.7%) ( P =0.005). Further, cholesterol efflux was significantly inversely associated with insulin sensitivity index ( P &lt;0.001), directly with arterial insulin concentration ( P &lt;0.001) and directly with cholesteryl ester transfer protein (CETP) mass ( P =0.044). Conclusion: Plasmas from overweight subjects with insulin resistance induced greater in vitro cholesterol efflux compared with IS subjects. Efflux inversely correlated with insulin sensitivity suggesting an increase in reverse cholesterol transport in the IR state that may lead to greater transfer of cholesterol to apoB lipoproteins from high-density lipoproteins via CETP as a factor in the association between IR and atherosclerosis.</description><identifier>ISSN: 0307-0565</identifier><identifier>EISSN: 1476-5497</identifier><identifier>DOI: 10.1038/ijo.2011.170</identifier><identifier>PMID: 21876547</identifier><identifier>CODEN: IJOBDP</identifier><language>eng</language><publisher>London: Nature Publishing Group UK</publisher><subject>Analysis ; Apolipoproteins ; Arteriosclerosis ; Atherosclerosis ; ATP Binding Cassette Transporter 1 ; ATP-Binding Cassette Transporters - metabolism ; Australia - epidemiology ; Biological and medical sciences ; Biological Transport ; Blood cholesterol ; Blood diseases ; Body mass index ; Body weight ; Cardiorespiratory ; Cardiovascular disease ; Cardiovascular diseases ; Cholesterol ; Cholesterol - metabolism ; Cholesterol Ester Transfer Proteins - metabolism ; Cholesteryl ester transfer protein ; Coronary Artery Disease - metabolism ; Coronary vessels ; Diabetes ; Disorders of blood lipids. Hyperlipoproteinemia ; Epidemiology ; Female ; Glucose tolerance ; Glucose Tolerance Test ; Health aspects ; Health Promotion and Disease Prevention ; Health risks ; High density lipoprotein ; Hormones ; Human subjects ; Humans ; Insulin ; Insulin - blood ; Insulin Resistance ; Internal Medicine ; Leptin ; Leptin - blood ; Lipids ; Lipoproteins ; Macrophages ; Macrophages - metabolism ; Male ; Mathematical models ; Measurement ; Medical sciences ; Medicine ; Medicine &amp; Public Health ; Metabolic Diseases ; Metabolic disorders ; Metabolic syndrome ; Metabolic Syndrome - complications ; Metabolic Syndrome - epidemiology ; Metabolic Syndrome - metabolism ; Middle Aged ; Miscellaneous ; Obesity ; Obesity - complications ; Obesity - epidemiology ; Obesity - metabolism ; original-article ; Other metabolic disorders ; Overweight ; Overweight persons ; Physiological aspects ; Plasma ; Public Health ; Risk Factors ; Vein &amp; artery diseases ; Women</subject><ispartof>International Journal of Obesity, 2012-03, Vol.36 (3), p.407-413</ispartof><rights>Macmillan Publishers Limited 2012</rights><rights>2015 INIST-CNRS</rights><rights>COPYRIGHT 2012 Nature Publishing Group</rights><rights>Copyright Nature Publishing Group Mar 2012</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c607t-37580225d06554b39e1ba92efc35d064cdc577d91b5397326b4e778020f836623</citedby><cites>FETCH-LOGICAL-c607t-37580225d06554b39e1ba92efc35d064cdc577d91b5397326b4e778020f836623</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,780,784,2725,27922,27923</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&amp;idt=25665919$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/21876547$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Nestel, P</creatorcontrib><creatorcontrib>Hoang, A</creatorcontrib><creatorcontrib>Sviridov, D</creatorcontrib><creatorcontrib>Straznicky, N</creatorcontrib><title>Cholesterol efflux from macrophages is influenced differentially by plasmas from overweight insulin-sensitive and -resistant subjects</title><title>International Journal of Obesity</title><addtitle>Int J Obes</addtitle><addtitle>Int J Obes (Lond)</addtitle><description>Objective: In vitro measurements of cholesterol efflux from macrophages have recently been shown to associate with cardiovascular risk. We investigated whether cholesterol efflux from macrophages incubated with plasmas from overweight/obese subjects with metabolic syndrome was influenced by the presence of insulin resistance. Methods: Plasmas were obtained from 47 men and women with metabolic syndrome, of whom 25 were found to be insulin resistant (IR) and 22 insulin sensitive (IS) (Matsuda, De Fronzo equation based on oral glucose tolerance test). Activated human macrophage THP-1 cells in which cholesterol had been radiolabelled were incubated with the subjects’ plasmas to allow calculation of % cholesterol efflux. Results: Body mass index and waist measurements, as well as plasma lipid levels, did not differ between the two groups. Homeostatic model assessment-insulin resistance value as well as plasma insulin and leptin concentrations were higher in IR subjects. Cholesterol efflux was found to be significantly greater with plasmas from IR subjects (9.1%) than from IS subjects (6.7%) ( P =0.005). Further, cholesterol efflux was significantly inversely associated with insulin sensitivity index ( P &lt;0.001), directly with arterial insulin concentration ( P &lt;0.001) and directly with cholesteryl ester transfer protein (CETP) mass ( P =0.044). Conclusion: Plasmas from overweight subjects with insulin resistance induced greater in vitro cholesterol efflux compared with IS subjects. Efflux inversely correlated with insulin sensitivity suggesting an increase in reverse cholesterol transport in the IR state that may lead to greater transfer of cholesterol to apoB lipoproteins from high-density lipoproteins via CETP as a factor in the association between IR and atherosclerosis.</description><subject>Analysis</subject><subject>Apolipoproteins</subject><subject>Arteriosclerosis</subject><subject>Atherosclerosis</subject><subject>ATP Binding Cassette Transporter 1</subject><subject>ATP-Binding Cassette Transporters - metabolism</subject><subject>Australia - epidemiology</subject><subject>Biological and medical sciences</subject><subject>Biological Transport</subject><subject>Blood cholesterol</subject><subject>Blood diseases</subject><subject>Body mass index</subject><subject>Body weight</subject><subject>Cardiorespiratory</subject><subject>Cardiovascular disease</subject><subject>Cardiovascular diseases</subject><subject>Cholesterol</subject><subject>Cholesterol - metabolism</subject><subject>Cholesterol Ester Transfer Proteins - metabolism</subject><subject>Cholesteryl ester transfer protein</subject><subject>Coronary Artery Disease - metabolism</subject><subject>Coronary vessels</subject><subject>Diabetes</subject><subject>Disorders of blood lipids. 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subjects Analysis
Apolipoproteins
Arteriosclerosis
Atherosclerosis
ATP Binding Cassette Transporter 1
ATP-Binding Cassette Transporters - metabolism
Australia - epidemiology
Biological and medical sciences
Biological Transport
Blood cholesterol
Blood diseases
Body mass index
Body weight
Cardiorespiratory
Cardiovascular disease
Cardiovascular diseases
Cholesterol
Cholesterol - metabolism
Cholesterol Ester Transfer Proteins - metabolism
Cholesteryl ester transfer protein
Coronary Artery Disease - metabolism
Coronary vessels
Diabetes
Disorders of blood lipids. Hyperlipoproteinemia
Epidemiology
Female
Glucose tolerance
Glucose Tolerance Test
Health aspects
Health Promotion and Disease Prevention
Health risks
High density lipoprotein
Hormones
Human subjects
Humans
Insulin
Insulin - blood
Insulin Resistance
Internal Medicine
Leptin
Leptin - blood
Lipids
Lipoproteins
Macrophages
Macrophages - metabolism
Male
Mathematical models
Measurement
Medical sciences
Medicine
Medicine & Public Health
Metabolic Diseases
Metabolic disorders
Metabolic syndrome
Metabolic Syndrome - complications
Metabolic Syndrome - epidemiology
Metabolic Syndrome - metabolism
Middle Aged
Miscellaneous
Obesity
Obesity - complications
Obesity - epidemiology
Obesity - metabolism
original-article
Other metabolic disorders
Overweight
Overweight persons
Physiological aspects
Plasma
Public Health
Risk Factors
Vein & artery diseases
Women
title Cholesterol efflux from macrophages is influenced differentially by plasmas from overweight insulin-sensitive and -resistant subjects
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