title: Adiponectin increases macrophages cholesterol efflux and suppresses foam cell formation in patients with type 2 diabetes mellitus.
abstract: OBJECTIVE
  Low levels of blood adiponectin contribute to an increased risk of cardiovascular disease (CVD) in patients with type 2 diabetes mellitus (T2DM). To determine the mechanism through which adiponectin deficiency mediates accelerated cardiovascular disease in patients with diabetes, we investigated the effects of adiponectin on macrophage cholesterol deposition.
  
  
  RESULTS
  35 diabetic patients and 35 nondiabetic healthy subjects were recruited in this study. Macrophages from patients with diabetes mellitus were cultured in adiponectin-free or adiponectin-supplemented media and exposed to oxidized low-density lipoprotein cholesterol (OxLDL). Adiponectin treatment markedly suppressed foam cell formation in OxLDL-treated macrophages from diabetic subjects only, which was mainly attributed to an increase in cholesterol efflux. Adiponectin treatment significantly increased ATP-binding cassette transporter (ABC) ABCG1 mRNA and protein levels but not ABCA1, without affecting protein expression of scavenger receptors, including scavenger receptor-A (SR-A) and CD36 in diabetics. Pharmacological or genetic inhibition of liver X receptor α (LXRα) blocks the adiponectin-mediated ABCG1 expression, suggesting that LXRα activation is necessary for the attenuation of lipid accumulation of macrophages by adiponectin. In addition, deletion of the adiponectin receptor (adipoR1) in macrophages from diabetic patients accelerated foam cell formation induced by OxLDL. Finally, a strong positive correlation was noted between decreased serum adiponectin levels and impaired cholesterol efflux capacity both before and after adjustment for HDL-C and ApoAI in diabetic patients (both P < 0.001).
  
  
  CONCLUSIONS
  The present study identifies reduced adiopoR signaling as a critical mechanism underlying increased foam cell formation and accelerated cardiovascular disease in diabetic subjects.
authors: Guangdong Provincial Key Laboratory of Food, Nutrition and Health, Department of Nutrition, School of Public Health, Sun Yat-sen University (Northern Campus), Guangzhou, Guangdong Province 510080, China.
authors: Min
authors: M
authors: Wang
authors: Duan
authors: D
authors: Wang
authors: Yuhua
authors: Y
authors: Zhang
authors: Xiaoming
authors: X
authors: Wang
authors: Yan
authors: Y
authors: Liu
authors: Min
authors: M
authors: Xia
mesh_terms: D000070998:ATP Binding Cassette Transporter, Subfamily G, Member 1; D018528:ATP-Binding Cassette Transporters / Q000235:genetics; D052242:Adiponectin / Q000378:metabolism* / Q000494:pharmacology; D000368:Aged; D000818:Animals; D018955:CD36 Antigens / Q000235:genetics; D002352:Carrier Proteins / Q000235:genetics; D002784:Cholesterol / Q000378:metabolism*; D003924:Diabetes Mellitus, Type 2 / Q000378:metabolism*; D005260:Female; D005487:Foam Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D006801:Humans; D008077:Lipoproteins, LDL / Q000378:metabolism; D000071518:Liver X Receptors; D008264:Macrophages / Q000166:cytology / Q000378:metabolism*; D017737:Macrophages, Peritoneal / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008817:Mice, Mutant Strains; D008875:Middle Aged; D057093:Orphan Nuclear Receptors / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D034741:RNA, Small Interfering / Q000235:genetics; D051122:Scavenger Receptors, Class B / Q000235:genetics; D000068103:Serine-Arginine Splicing Factors; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology
chemical_list: C419353:ABCG1 protein, human; C499918:ADIPOQ protein, human; D000070998:ATP Binding Cassette Transporter, Subfamily G, Member 1; D018528:ATP-Binding Cassette Transporters; D052242:Adiponectin; D018955:CD36 Antigens; D002352:Carrier Proteins; D008077:Lipoproteins, LDL; D000071518:Liver X Receptors; C000605213:NR1H3 protein, human; C000605214:Nr1h3 protein, mouse; D057093:Orphan Nuclear Receptors; D012333:RNA, Messenger; D034741:RNA, Small Interfering; C503566:SCAF1 protein, human; C495124:SCARB1 protein, human; D051122:Scavenger Receptors, Class B; C099252:oxidized low density lipoprotein; D000068103:Serine-Arginine Splicing Factors; D002784:Cholesterol