title: Effects of Exendin-4 on human adipose tissue inflammation and ECM remodelling.
abstract: Subjects with type-2 diabetes are typically obese with dysfunctional adipose tissue (AT). Glucagon-like peptide-1 (GLP-1) analogues are routinely used to improve glycaemia. Although, they also aid weight loss that improves AT function, their direct effect on AT function is unclear. To explore GLP-1 analogues' influence on human AT's cytokine and extracellular matrix (ECM) regulation, we therefore obtained and treated omental (OMAT) and subcutaneous (SCAT) AT samples with Exendin-4, an agonist of the GLP-1 receptor (GLP-1R).
  
  
  
  OMAT and abdominal SCAT samples obtained from women during elective surgery at the Royal Devon & Exeter Hospital (UK) were treated with increasing doses of Exendin-4. Changes in RNA expression of adipokines, inflammatory cytokines, ECM components and their regulators were assessed and protein secretion analysed by ELISA. GLP-1R protein accumulation was compared in paired AT depot samples.
  
  
  
  Exendin-4 induced an increase in OMAT adiponectin (P=0.02) and decrease in elastin expression (P=0.03) in parallel with reduced elastin secretion (P=0.04). In contrast to OMAT, we did not observe an effect on SCAT. There was no change in the expression of inflammatory markers (CD14, TNFA, MCP-1), collagens, TGFB1 or CTGF. GLP-1R accumulation was higher in SCAT.
  
  
  
  Independently of weight loss, which may bias findings of in vivo studies, GLP-1 analogues modify human OMAT physiology favourably by increasing the insulin-sensitising cytokine adiponectin. However, the reduction of elastin and no apparent effect on AT's inflammatory cytokines suggest that GLP-1 analogues may be less beneficial to AT function, especially if there is no associated weight loss.
authors.affiliation: Diabetes and Obesity Research Group, University of Exeter Medical School, Exeter, UK.
authors.forename: E
authors.initials: E
authors.lastname: Pastel
authors.affiliation: Diabetes and Obesity Research Group, University of Exeter Medical School, Exeter, UK.
authors.forename: S
authors.initials: S
authors.lastname: Joshi
authors.affiliation: NIHR Exeter Clinical Research Facility, University of Exeter Medical School, Exeter, UK.|RD&E NHS Foundation trust, Exeter, UK.
authors.forename: B
authors.initials: B
authors.lastname: Knight
authors.affiliation: RD&E NHS Foundation trust, Exeter, UK.
authors.forename: N
authors.initials: N
authors.lastname: Liversedge
authors.affiliation: Diabetes and Obesity Research Group, University of Exeter Medical School, Exeter, UK.
authors.forename: R
authors.initials: R
authors.lastname: Ward
authors.affiliation: Diabetes and Obesity Research Group, University of Exeter Medical School, Exeter, UK.
authors.forename: K
authors.initials: K
authors.lastname: Kos
mesh_terms: D054392:Adipokines / Q000235:genetics / Q000378:metabolism*; D052242:Adiponectin / Q000235:genetics / Q000378:metabolism; D000273:Adipose Tissue / Q000187:drug effects* / Q000378:metabolism; D000368:Aged; D016207:Cytokines / Q000235:genetics / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D004549:Elastin / Q000235:genetics / Q000378:metabolism; D000077270:Exenatide; D005109:Extracellular Matrix / Q000187:drug effects* / Q000378:metabolism; D005260:Female; D006801:Humans; D054795:Incretins / Q000494:pharmacology*; D007249:Inflammation / Q000378:metabolism*; D008875:Middle Aged; D050177:Overweight / Q000378:metabolism; D010455:Peptides / Q000494:pharmacology*; D014688:Venoms / Q000494:pharmacology*; D000097789:Glucagon-Like Peptide-1 Receptor Agonists
chemical_list: D054392:Adipokines; D052242:Adiponectin; D016207:Cytokines; D054795:Incretins; D010455:Peptides; D014688:Venoms; D004549:Elastin; D000077270:Exenatide; D000097789:Glucagon-Like Peptide-1 Receptor Agonists