title: Diet induction of monocyte chemoattractant protein-1 and its impact on obesity.
abstract: OBJECTIVE
  To examine the effect of a high-fat diet on gene expression in adipose tissues and to determine induction kinetics of adipose monocyte chemoattractant protein-1 and -3 (MCP-1 and MCP-3) in diet-induced obesity (DIO) and the effect of a lack of MCP-1 signaling on DIO susceptibility and macrophage recruitment into adipose tissue.
  
  
  METHODS
  Obese and lean adipose tissues were profiled for expression changes. The time-course of MCP-1 and MCP-3 expression was examined by reverse transcriptase-polymerase chain reaction. Plasma MCP-1 levels were determined by enzyme-linked immunosorbent assay (ELISA). Chemokine receptor-2 (CCR2) knockout mice were placed on the high-fat diet to determine DIO susceptibility. Macrophage infiltration in adipose tissue was examined by immunohistochemistry with F4/80 antibody.
  
  
  RESULTS
  DIO elevated adipose expression of many inflammatory genes, including MCP-1 and MCP-3. Adipose MCP-1 and MCP-3 mRNA levels increased within 7 days of starting a high-fat diet, with elevation of plasma MCP-1 detected after 4 weeks on the diet. The induction of MCP-1 and MCP-3 expression preceded that of tumor necrosis factor-alpha. The elevated plasma MCP-1 concentration in obese mice was partially reversed by treatment with AM251. No change in DIO susceptibility and macrophage accumulation in adipose tissue were observed in CCR2 knockout mice, which lack the MCP-1 receptor CCR2.
  
  
  CONCLUSIONS
  A high-fat diet elevated adipose expression of inflammatory genes, including early induction of MCP-1 and MCP-3, supporting the view that obese adipose tissues contribute to systemic inflammation. However, despite increased MCP-1 in obesity, disruption of MCP-1 signaling did not confer resistance to DIO in mice or reduce adipose tissue macrophage infiltration.
authors.affiliation: Department of Metabolic Disorders, Merck Research Laboratories, Rahway, NJ 07065, USA.
authors.forename: Airu
authors.initials: A
authors.lastname: Chen
authors.forename: Sheena
authors.initials: S
authors.lastname: Mumick
authors.forename: Chunsheng
authors.initials: C
authors.lastname: Zhang
authors.forename: John
authors.initials: J
authors.lastname: Lamb
authors.forename: Hongyue
authors.initials: H
authors.lastname: Dai
authors.forename: Drew
authors.initials: D
authors.lastname: Weingarth
authors.forename: John
authors.initials: J
authors.lastname: Mudgett
authors.forename: Howard
authors.initials: H
authors.lastname: Chen
authors.forename: Douglas J
authors.initials: DJ
authors.lastname: MacNeil
authors.forename: Marc L
authors.initials: ML
authors.lastname: Reitman
authors.forename: Su
authors.initials: S
authors.lastname: Qian
mesh_terms: D017667:Adipocytes / Q000378:metabolism; D000818:Animals; D015703:Antigens, CD / Q000096:biosynthesis / Q000235:genetics; D015214:Antigens, Differentiation, Myelomonocytic / Q000096:biosynthesis / Q000235:genetics; D043422:Carboxypeptidases A / Q000096:biosynthesis / Q000235:genetics; D018932:Chemokine CCL2 / Q000096:biosynthesis* / Q000235:genetics; D004041:Dietary Fats / Q000008:administration & dosage*; D020869:Gene Expression Profiling; D018836:Inflammation Mediators / Q000378:metabolism; D008264:Macrophages / Q000473:pathology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009765:Obesity / Q000209:etiology* / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D054390:Receptors, CCR2; D019707:Receptors, Chemokine / Q000172:deficiency / Q000235:genetics; D015398:Signal Transduction; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis / Q000235:genetics; D000097382:CD68 Molecule
chemical_list: D015703:Antigens, CD; D015214:Antigens, Differentiation, Myelomonocytic; D043422:Carboxypeptidases A; D018932:Chemokine CCL2; D004041:Dietary Fats; D018836:Inflammation Mediators; D012333:RNA, Messenger; D054390:Receptors, CCR2; D019707:Receptors, Chemokine; D014409:Tumor Necrosis Factor-alpha; C081026:CD68 protein, mouse; D000097382:CD68 Molecule; C491768:Ccl2 protein, mouse; C515335:Ccr2 protein, mouse; C503326:Cpa3 protein, mouse