title: Adipose and Circulating CCL18 Levels Associate With Metabolic Risk Factors in Women.
abstract: BACKGROUND
  Cardiometabolic complications in obesity may be linked to white adipose tissue (WAT) dysfunction. Transcriptomic studies of Sc WAT have reported that CCL18, encoding the CC chemokine ligand 18 (CCL18), is increased in obesity/insulin resistance but its functional role is unknown.
  
  
  OBJECTIVE
  Our objectives were to determine if CCL18 is secreted from Sc WAT and if secreted and/or serum levels associate with metabolic phenotypes. We also planned to define the primary cellular source and if CCL18 exerts effects on adipocytes.
  
  
  METHODS
  This is a cohort study.
  
  
  METHODS
  The study took place in an outpatient academic clinic.
  
  
  METHODS
  A total of 130 obese women scheduled for bariatric surgery and 35 nonobese controls were included.
  
  
  METHODS
  Insulin sensitivity was assessed by hyperinsulinemic euglycemic clamp or homeostasis model assessment. CCL18 was analyzed in serum/WAT incubates by ELISA. Effects of recombinant CCL18 was determined in cultures of primary human adipocytes and the monocyte cell line THP-1 differentiated into M0/M1/M2 macrophages.
  
  
  METHODS
  Association with metabolic risk factors was measured.
  
  
  RESULTS
  CCL18 was secreted from WAT and the levels correlated positively with insulin resistance, Adult Treatment Panel III risk score and plasma triglycerides, independent of body mass index and better than other established adipocytokines. In 80 obese women, S-CCL18 levels were significantly higher in insulin resistant compared with insulin sensitive subjects. In WAT CCL18 mRNA was expressed in macrophages and correlated positively with immune-related genes, particularly those enriched in M2 macrophages. While CCL18 increased cyto-/chemokine expression in M0/M2-THP-1 cells, human adipocytes showed no responses in vitro.
  
  
  CONCLUSIONS
  Circulating and WAT-secreted CCL18 correlates with insulin resistance and metabolic risk score. Because CCL18 is macrophage-specific and associates with adipose immune gene expression, it may constitute a marker of WAT inflammation.
authors.affiliation: Department of Medicine (H7) (D.E.H., P.P., J.B., I.D., J.L., J.A., A.E., A.K., N.M., D.P.A., P.A., M.R.), Karolinska Institutet, Stockholm, Sweden; Department of Biosciences and Nutrition (H.G.), Karolinska Institutet, Huddinge, Sweden; Department of Clinical Sciences (E.N.), Karolinska Institutet, Danderyd Hospital, Danderyd, Sweden.
authors.forename: Daniel
authors.initials: D
authors.lastname: Eriksson Hogling
authors.affiliation: Department of Medicine (H7) (D.E.H., P.P., J.B., I.D., J.L., J.A., A.E., A.K., N.M., D.P.A., P.A., M.R.), Karolinska Institutet, Stockholm, Sweden; Department of Biosciences and Nutrition (H.G.), Karolinska Institutet, Huddinge, Sweden; Department of Clinical Sciences (E.N.), Karolinska Institutet, Danderyd Hospital, Danderyd, Sweden.
authors.forename: Paul
authors.initials: P
authors.lastname: Petrus
authors.affiliation: Department of Medicine (H7) (D.E.H., P.P., J.B., I.D., J.L., J.A., A.E., A.K., N.M., D.P.A., P.A., M.R.), Karolinska Institutet, Stockholm, Sweden; Department of Biosciences and Nutrition (H.G.), Karolinska Institutet, Huddinge, Sweden; Department of Clinical Sciences (E.N.), Karolinska Institutet, Danderyd Hospital, Danderyd, Sweden.
authors.forename: Hui
authors.initials: H
authors.lastname: Gao
authors.affiliation: Department of Medicine (H7) (D.E.H., P.P., J.B., I.D., J.L., J.A., A.E., A.K., N.M., D.P.A., P.A., M.R.), Karolinska Institutet, Stockholm, Sweden; Department of Biosciences and Nutrition (H.G.), Karolinska Institutet, Huddinge, Sweden; Department of Clinical Sciences (E.N.), Karolinska Institutet, Danderyd Hospital, Danderyd, Sweden.
authors.forename: Jesper
authors.initials: J
authors.lastname: Bäckdahl
authors.affiliation: Department of Medicine (H7) (D.E.H., P.P., J.B., I.D., J.L., J.A., A.E., A.K., N.M., D.P.A., P.A., M.R.), Karolinska Institutet, Stockholm, Sweden; Department of Biosciences and Nutrition (H.G.), Karolinska Institutet, Huddinge, Sweden; Department of Clinical Sciences (E.N.), Karolinska Institutet, Danderyd Hospital, Danderyd, Sweden.
authors.forename: Ingrid
authors.initials: I
authors.lastname: Dahlman
authors.affiliation: Department of Medicine (H7) (D.E.H., P.P., J.B., I.D., J.L., J.A., A.E., A.K., N.M., D.P.A., P.A., M.R.), Karolinska Institutet, Stockholm, Sweden; Department of Biosciences and Nutrition (H.G.), Karolinska Institutet, Huddinge, Sweden; Department of Clinical Sciences (E.N.), Karolinska Institutet, Danderyd Hospital, Danderyd, Sweden.
authors.forename: Jurga
authors.initials: J
authors.lastname: Laurencikiene
authors.affiliation: Department of Medicine (H7) (D.E.H., P.P., J.B., I.D., J.L., J.A., A.E., A.K., N.M., D.P.A., P.A., M.R.), Karolinska Institutet, Stockholm, Sweden; Department of Biosciences and Nutrition (H.G.), Karolinska Institutet, Huddinge, Sweden; Department of Clinical Sciences (E.N.), Karolinska Institutet, Danderyd Hospital, Danderyd, Sweden.
authors.forename: Juan
authors.initials: J
authors.lastname: Acosta
authors.affiliation: Department of Medicine (H7) (D.E.H., P.P., J.B., I.D., J.L., J.A., A.E., A.K., N.M., D.P.A., P.A., M.R.), Karolinska Institutet, Stockholm, Sweden; Department of Biosciences and Nutrition (H.G.), Karolinska Institutet, Huddinge, Sweden; Department of Clinical Sciences (E.N.), Karolinska Institutet, Danderyd Hospital, Danderyd, Sweden.
authors.forename: Anna
authors.initials: A
authors.lastname: Ehrlund
authors.affiliation: Department of Medicine (H7) (D.E.H., P.P., J.B., I.D., J.L., J.A., A.E., A.K., N.M., D.P.A., P.A., M.R.), Karolinska Institutet, Stockholm, Sweden; Department of Biosciences and Nutrition (H.G.), Karolinska Institutet, Huddinge, Sweden; Department of Clinical Sciences (E.N.), Karolinska Institutet, Danderyd Hospital, Danderyd, Sweden.
authors.forename: Erik
authors.initials: E
authors.lastname: Näslund
authors.affiliation: Department of Medicine (H7) (D.E.H., P.P., J.B., I.D., J.L., J.A., A.E., A.K., N.M., D.P.A., P.A., M.R.), Karolinska Institutet, Stockholm, Sweden; Department of Biosciences and Nutrition (H.G.), Karolinska Institutet, Huddinge, Sweden; Department of Clinical Sciences (E.N.), Karolinska Institutet, Danderyd Hospital, Danderyd, Sweden.
authors.forename: Agne
authors.initials: A
authors.lastname: Kulyte
authors.affiliation: Department of Medicine (H7) (D.E.H., P.P., J.B., I.D., J.L., J.A., A.E., A.K., N.M., D.P.A., P.A., M.R.), Karolinska Institutet, Stockholm, Sweden; Department of Biosciences and Nutrition (H.G.), Karolinska Institutet, Huddinge, Sweden; Department of Clinical Sciences (E.N.), Karolinska Institutet, Danderyd Hospital, Danderyd, Sweden.
authors.forename: Niklas
authors.initials: N
authors.lastname: Mejhert
authors.affiliation: Department of Medicine (H7) (D.E.H., P.P., J.B., I.D., J.L., J.A., A.E., A.K., N.M., D.P.A., P.A., M.R.), Karolinska Institutet, Stockholm, Sweden; Department of Biosciences and Nutrition (H.G.), Karolinska Institutet, Huddinge, Sweden; Department of Clinical Sciences (E.N.), Karolinska Institutet, Danderyd Hospital, Danderyd, Sweden.
authors.forename: Daniel P
authors.initials: DP
authors.lastname: Andersson
authors.affiliation: Department of Medicine (H7) (D.E.H., P.P., J.B., I.D., J.L., J.A., A.E., A.K., N.M., D.P.A., P.A., M.R.), Karolinska Institutet, Stockholm, Sweden; Department of Biosciences and Nutrition (H.G.), Karolinska Institutet, Huddinge, Sweden; Department of Clinical Sciences (E.N.), Karolinska Institutet, Danderyd Hospital, Danderyd, Sweden.
authors.forename: Peter
authors.initials: P
authors.lastname: Arner
authors.affiliation: Department of Medicine (H7) (D.E.H., P.P., J.B., I.D., J.L., J.A., A.E., A.K., N.M., D.P.A., P.A., M.R.), Karolinska Institutet, Stockholm, Sweden; Department of Biosciences and Nutrition (H.G.), Karolinska Institutet, Huddinge, Sweden; Department of Clinical Sciences (E.N.), Karolinska Institutet, Danderyd Hospital, Danderyd, Sweden.
authors.forename: Mikael
authors.initials: M
authors.lastname: Rydén
mesh_terms: D050154:Adiposity; D000328:Adult; D050110:Bariatric Surgery; D015415:Biomarkers / Q000097:blood / Q000378:metabolism; D015992:Body Mass Index; D002460:Cell Line; D002478:Cells, Cultured; D019742:Chemokines, CC / Q000097:blood / Q000235:genetics / Q000378:metabolism*; D015331:Cohort Studies; D005260:Female; D005786:Gene Expression Regulation; D063990:Gene Ontology; D006801:Humans; D015228:Hypertriglyceridemia / Q000209:etiology; D007333:Insulin Resistance; D008264:Macrophages / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D024821:Metabolic Syndrome / Q000453:epidemiology / Q000209:etiology*; D009767:Obesity, Morbid / Q000276:immunology / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D015434:Panniculitis / Q000209:etiology*; D011994:Recombinant Proteins / Q000378:metabolism; D012307:Risk Factors; D050507:Subcutaneous Fat, Abdominal / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D013548:Sweden / Q000453:epidemiology
chemical_list: D015415:Biomarkers; C111792:CCL18 protein, human; D019742:Chemokines, CC; D011994:Recombinant Proteins