title: Enhanced adiponectin actions by overexpression of adiponectin receptor 1 in macrophages.
abstract: OBJECTIVE
  Adiponectin is one of several important, metabolically active cytokines secreted from adipose tissue. Epidemiologic studies have associated low circulating levels of this adipokine with multiple metabolic disorders including obesity, insulin resistance, type II diabetes, and cardiovascular disease. To investigate how enhanced adiponectin-mediated changes in metabolism in vivo, we generated transgenic mice which specifically overexpress the gene coding for adiponectin receptor 1 (AdipoR1) in mouse macrophages using the human scavenger receptor A-I gene (SR-AI) enhancer/promoter. We found that macrophage-specific AdipoR1 transgenic mice (AdR1-TG) presented reduced whole body weight, fat accumulation and liver steatosis when these transgenic mice were fed with a high fat diet. Moreover, these macrophage AdR1-TG mice exhibited enhanced whole-body glucose tolerance and insulin sensitivity with reduced proinflammatory cytokines, MCP-1 and TNF-α, both in the serum and in the insulin target metabolic tissues. Additional studies demonstrated that these macrophage AdR1-TG animals exhibited reduced macrophage foam cell formation in the arterial wall when these transgenic mice were crossed with a low-density lipoprotein receptor (Ldlr) deficient mouse model.
  
  
  CONCLUSIONS
  These results suggest that AdipoR1 overexpressed in macrophages can physiologically modulate metabolic activities in vivo by enhancing adiponectin actions in distal metabolically active tissues. The AdipoR1 modified macrophages provide unique interactions with the residented tissues/cells, suggesting a novel role of macrophage adiponectin receptor in improving metabolic disorders in vivo.
authors.affiliation: Department of Nutrition Sciences, University of Alabama at Birmingham, Birmingham, AL 35294-3360, USA.
authors.forename: Nanlan
authors.initials: N
authors.lastname: Luo
authors.forename: B Hong
authors.initials: BH
authors.lastname: Chung
authors.forename: Xiangdong
authors.initials: X
authors.lastname: Wang
authors.forename: Richard L
authors.initials: RL
authors.lastname: Klein
authors.forename: Chao-Ke
authors.initials: CK
authors.lastname: Tang
authors.forename: W Timothy
authors.initials: WT
authors.lastname: Garvey
authors.forename: Yuchang
authors.initials: Y
authors.lastname: Fu
mesh_terms: D052242:Adiponectin / Q000097:blood; D000273:Adipose Tissue / Q000378:metabolism; D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D002352:Carrier Proteins / Q000235:genetics; D002478:Cells, Cultured; D002784:Cholesterol / Q000097:blood; D004195:Disease Models, Animal; D005234:Fatty Liver / Q000235:genetics / Q000378:metabolism; D005487:Foam Cells / Q000166:cytology / Q000502:physiology; D018149:Glucose Intolerance / Q000235:genetics / Q000378:metabolism; D006801:Humans; D007249:Inflammation / Q000235:genetics / Q000378:metabolism; D007328:Insulin / Q000097:blood; D008099:Liver / Q000378:metabolism; D017737:Macrophages, Peritoneal / Q000166:cytology / Q000502:physiology*; D024821:Metabolic Syndrome / Q000235:genetics* / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D018482:Muscle, Skeletal / Q000378:metabolism; D011401:Promoter Regions, Genetic / Q000235:genetics; D054419:Receptors, Adiponectin / Q000235:genetics* / Q000378:metabolism*; D000068103:Serine-Arginine Splicing Factors; D014280:Triglycerides / Q000097:blood
chemical_list: D052242:Adiponectin; C499919:Adipoq protein, mouse; D001786:Blood Glucose; D002352:Carrier Proteins; D007328:Insulin; D054419:Receptors, Adiponectin; C503566:SCAF1 protein, human; D014280:Triglycerides; C475419:adiponectin receptor 1, mouse; D000068103:Serine-Arginine Splicing Factors; D002784:Cholesterol