title: Interleukin-6 induces impairment in human subcutaneous adipogenesis in obesity-associated insulin resistance.
abstract: A subset of obese individuals remains insulin sensitive by mechanisms as yet unclear. The hypothesis that maintenance of normal subcutaneous (SC) adipogenesis accounts, at least partially, for this protective phenotype and whether it can be abrogated by chronic exposure to IL-6 was investigated.
  
  
  
  Adipose tissue biopsies were collected from insulin-sensitive (IS) and insulin-resistant (IR) individuals undergoing weight-reduction surgery. Adipocyte size, pre-adipocyte proportion of stromal vascular fraction (SVF)-derived cells, adipogenic capacity and gene expression profiles of isolated pre-adipocytes were determined, along with local in vitro IL-6 secretion. Adipogenic capacity was further assessed in response to exogenous IL-6 application.
  
  
  
  Despite being equally obese, IR individuals had significantly lower plasma leptin and adiponectin levels and higher IL-6 levels compared with age-matched IS counterparts. Elevated systemic IL-6 in IR individuals was associated with hyperplasia of adipose tissue-derived SVF cells, despite higher frequency of hypertrophied adipocytes. SC pre-adipocytes from these tissues exhibited lower adipogenic capacity accompanied by downregulation of PPARγ (also known as PPARG) and CEBPα (also known as CEBPA) and upregulation of GATA3 expression. Impaired adipogenesis in IR individuals was further associated with increased adipose secretion of IL-6. Treatment of IS-derived SC pre-adipocytes with IL-6 reduced their adipogenic capacity to levels of the IR group.
  
  
  
  Obesity-associated insulin resistance is marked by impaired SC adipogenesis, mediated, at least in a subset of individuals, by elevated local levels of IL-6. Understanding the molecular mechanisms underlying reduced adipogenic capacity in IR individuals could help target appropriate therapeutic strategies aimed at those at greatest risk of insulin resistance and type 2 diabetes mellitus.
authors.affiliation: Anti-Doping Lab Qatar, Sports City Road, P.O. Box 27775, Doha, Qatar.|School of Cellular and Molecular Medicine, University of Bristol, Bristol, UK.
authors.forename: Shamma
authors.initials: S
authors.lastname: Almuraikhy
authors.affiliation: School of Cellular and Molecular Medicine, University of Bristol, Bristol, UK.
authors.forename: Wael
authors.initials: W
authors.lastname: Kafienah
authors.affiliation: Bariatric and Metabolic Surgery, Hamad Medical Corporation, Doha, Qatar.
authors.forename: Moataz
authors.initials: M
authors.lastname: Bashah
authors.affiliation: Department of Physiology and Biophysics, Weill Cornell Medicine Qatar, Doha, Qatar.
authors.forename: Ilhame
authors.initials: I
authors.lastname: Diboun
authors.affiliation: Anti-Doping Lab Qatar, Sports City Road, P.O. Box 27775, Doha, Qatar.
authors.forename: Morana
authors.initials: M
authors.lastname: Jaganjac
authors.affiliation: Anti-Doping Lab Qatar, Sports City Road, P.O. Box 27775, Doha, Qatar.
authors.forename: Fatima
authors.initials: F
authors.lastname: Al-Khelaifi
authors.affiliation: Microbiology and Immunology, Weill Cornell Medicine Qatar, Doha, Qatar.
authors.forename: Houari
authors.initials: H
authors.lastname: Abdesselem
authors.affiliation: Microbiology and Immunology, Weill Cornell Medicine Qatar, Doha, Qatar.
authors.forename: Nayef A
authors.initials: NA
authors.lastname: Mazloum
authors.affiliation: Anti-Doping Lab Qatar, Sports City Road, P.O. Box 27775, Doha, Qatar.
authors.forename: Mohammed
authors.initials: M
authors.lastname: Alsayrafi
authors.affiliation: Anti-Doping Lab Qatar, Sports City Road, P.O. Box 27775, Doha, Qatar.
authors.forename: Vidya
authors.initials: V
authors.lastname: Mohamed-Ali
authors.affiliation: Anti-Doping Lab Qatar, Sports City Road, P.O. Box 27775, Doha, Qatar. melrayess@adlqatar.qa.
authors.forename: Mohamed A
authors.initials: MA
authors.lastname: Elrayess
mesh_terms: D017667:Adipocytes / Q000378:metabolism; D050156:Adipogenesis / Q000235:genetics / Q000502:physiology*; D052242:Adiponectin / Q000235:genetics / Q000378:metabolism; D000328:Adult; D003924:Diabetes Mellitus, Type 2 / Q000235:genetics / Q000378:metabolism; D005260:Female; D050990:GATA3 Transcription Factor / Q000235:genetics / Q000378:metabolism; D006801:Humans; D066298:In Vitro Techniques; D007333:Insulin Resistance / Q000235:genetics / Q000502:physiology*; D015850:Interleukin-6 / Q000235:genetics / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D009765:Obesity / Q000235:genetics / Q000378:metabolism*; D047495:PPAR gamma / Q000235:genetics / Q000378:metabolism
chemical_list: C499918:ADIPOQ protein, human; D052242:Adiponectin; D050990:GATA3 Transcription Factor; C494749:GATA3 protein, human; C508600:IL6 protein, human; D015850:Interleukin-6; D047495:PPAR gamma
keywords: Adipogenesis; Insulin resistance; Insulin sensitivity; Interleukin-6; Obesity; Subcutaneous fat; Type 2 diabetes mellitus