title: Expression of CD68 and macrophage chemoattractant protein-1 genes in human adipose and muscle tissues: association with cytokine expression, insulin resistance, and reduction by pioglitazone.
abstract: To examine the role of adipose-resident macrophages in insulin resistance, we examined the gene expression of CD68, a macrophage marker, along with macrophage chemoattractant protein-1 (MCP-1) in human subcutaneous adipose tissue using real-time RT-PCR. Both CD68 and MCP-1 mRNAs were expressed in human adipose tissue, primarily in the stromal vascular fraction. When measured in the adipose tissue from subjects with normal glucose tolerance, covering a wide range of BMI (21-51 kg/m2) and insulin sensitivity (S(I)) (0.6-8.0 x 10(-4)min(-1).microU(-1).ml(-1)), CD68 mRNA abundance, which correlated with the number of CD68-positive cells by immunohistochemistry, tended to increase with BMI but was not statistically significant. However, there was a significant inverse relation between CD68 mRNA and S(I) (r=-0.55, P=0.02). In addition, there was a strong positive relationship among adipose tissue CD68 mRNA, tumor necrosis factor-alpha (TNF-alpha) secretion in vitro (r=0.79, P<0.005), and plasma interleukin-6 (r=0.67, P < 0.005). To determine whether improving S(I) in subjects with impaired glucose tolerance (IGT) was associated with decreased CD68 expression, IGT subjects were treated for 10 weeks with pioglitazone or metformin. Pioglitazone increased S(I) by 60% and in the same subjects reduced both CD68 and MCP-1 mRNAs by >50%. Furthermore, pioglitazone resulted in a reduction in the number of CD68-positive cells in adipose tissue and reduced plasma TNF-alpha. Metformin had no effect on any of these measures. Thus, treatment with pioglitazone reduces expression of CD68 and MCP-1 in adipose tissue, apparently by reducing macrophage numbers, resulting in reduced inflammatory cytokine production and improvement in S(I).
authors.affiliation: Research, Central Arkansas Veterans Healthcare System, 598/151 LR, 4300 West 7th St., Little Rock, AR 72205, USA. kernphilipa@uams.edu
authors.forename: Gina B
authors.initials: GB
authors.lastname: Di Gregorio
authors.forename: Aiwei
authors.initials: A
authors.lastname: Yao-Borengasser
authors.forename: Neda
authors.initials: N
authors.lastname: Rasouli
authors.forename: Vijayalakshmi
authors.initials: V
authors.lastname: Varma
authors.forename: Tong
authors.initials: T
authors.lastname: Lu
authors.forename: Leslie M
authors.initials: LM
authors.lastname: Miles
authors.forename: Gouri
authors.initials: G
authors.lastname: Ranganathan
authors.forename: Charlotte A
authors.initials: CA
authors.lastname: Peterson
authors.forename: Robert E
authors.initials: RE
authors.lastname: McGehee
authors.forename: Philip A
authors.initials: PA
authors.lastname: Kern
mesh_terms: D000273:Adipose Tissue / Q000737:chemistry*; D000328:Adult; D015703:Antigens, CD / Q000235:genetics*; D015214:Antigens, Differentiation, Myelomonocytic / Q000235:genetics*; D002452:Cell Count; D018932:Chemokine CCL2 / Q000235:genetics*; D016207:Cytokines / Q000097:blood / Q000235:genetics*; D015870:Gene Expression; D006801:Humans; D007004:Hypoglycemic Agents / Q000008:administration & dosage; D007333:Insulin Resistance; D008264:Macrophages; D008687:Metformin / Q000008:administration & dosage; D008875:Middle Aged; D009132:Muscles / Q000737:chemistry; D009765:Obesity / Q000378:metabolism; D000077205:Pioglitazone; D012333:RNA, Messenger / Q000032:analysis; D020133:Reverse Transcriptase Polymerase Chain Reaction; D045162:Thiazolidinediones / Q000008:administration & dosage*; D000097382:CD68 Molecule
chemical_list: D015703:Antigens, CD; D015214:Antigens, Differentiation, Myelomonocytic; D018932:Chemokine CCL2; D016207:Cytokines; D007004:Hypoglycemic Agents; D008687:Metformin; D000077205:Pioglitazone; D012333:RNA, Messenger; D045162:Thiazolidinediones; C111835:CCL2 protein, human; C067980:CD68 antigen, human; D000097382:CD68 Molecule