title: Increased adipose tissue oxygen tension in obese compared with lean men is accompanied by insulin resistance, impaired adipose tissue capillarization, and inflammation.
abstract: BACKGROUND
  Adipose tissue (AT) dysfunction in obesity contributes to chronic, low-grade inflammation that predisposes to type 2 diabetes mellitus and cardiovascular disease. Recent in vitro studies suggest that AT hypoxia may induce inflammation. We hypothesized that adipose tissue blood flow (ATBF) regulates AT oxygen partial pressure (AT P(O2)), thereby affecting AT inflammation and insulin sensitivity.
  
  
  RESULTS
  We developed an optochemical measurement system for continuous monitoring of AT P(O2) using microdialysis. The effect of alterations in ATBF on AT P(O2) was investigated in lean and obese subjects with both pharmacological and physiological approaches to manipulate ATBF. Local administration of angiotensin II (vasoconstrictor) in abdominal subcutaneous AT decreased ATBF and AT P(O2), whereas infusion of isoprenaline (vasodilator) evoked opposite effects. Ingestion of a glucose drink increased ATBF and AT P(O2) in lean subjects, but these responses were blunted in obese individuals. However, AT P(O2) was higher (hyperoxia) in obese subjects despite lower ATBF, which appears to be explained by lower AT oxygen consumption. This was accompanied by insulin resistance, lower AT capillarization, lower AT expression of genes encoding proteins involved in mitochondrial biogenesis and function, and higher AT gene expression of macrophage infiltration and inflammatory markers.
  
  
  CONCLUSIONS
  Our findings establish ATBF as an important regulator of AT P(O2). Nevertheless, obese individuals exhibit AT hyperoxia despite lower ATBF, which seems to be explained by lower AT oxygen consumption. This is accompanied by insulin resistance, impaired AT capillarization, and higher AT gene expression of inflammatory cell markers.
  
  
  BACKGROUND
  http://www.trialregister.nl. Unique identifier: NTR2451.
authors.affiliation: Department of Human Biology, NUTRIM School for Nutrition, Toxicology, and Metabolism, Maastricht University Medical Centre, PO Box 616, 6200 MD Maastricht, Netherlands. G.Goossens@maastrichtuniversity.nl
authors.forename: Gijs H
authors.initials: GH
authors.lastname: Goossens
authors.forename: Alessandro
authors.initials: A
authors.lastname: Bizzarri
authors.forename: Nicolas
authors.initials: N
authors.lastname: Venteclef
authors.forename: Yvonne
authors.initials: Y
authors.lastname: Essers
authors.forename: Jack P
authors.initials: JP
authors.lastname: Cleutjens
authors.forename: Ellen
authors.initials: E
authors.lastname: Konings
authors.forename: Johan W E
authors.initials: JW
authors.lastname: Jocken
authors.forename: Merima
authors.initials: M
authors.lastname: Cajlakovic
authors.forename: Volker
authors.initials: V
authors.lastname: Ribitsch
authors.forename: Karine
authors.initials: K
authors.lastname: Clément
authors.forename: Ellen E
authors.initials: EE
authors.lastname: Blaak
mesh_terms: D000273:Adipose Tissue / Q000098:blood supply* / Q000378:metabolism* / Q000503:physiopathology; D000804:Angiotensin II / Q000494:pharmacology; D006801:Humans; D018496:Hyperoxia / Q000503:physiopathology; D007249:Inflammation / Q000378:metabolism* / Q000503:physiopathology; D007333:Insulin Resistance / Q000502:physiology*; D007545:Isoproterenol / Q000494:pharmacology; D008297:Male; D008833:Microcirculation / Q000187:drug effects / Q000502:physiology; D008875:Middle Aged; D008928:Mitochondria / Q000502:physiology; D009765:Obesity / Q000378:metabolism* / Q000503:physiopathology; D010100:Oxygen / Q000378:metabolism*; D010101:Oxygen Consumption / Q000502:physiology; D012039:Regional Blood Flow / Q000187:drug effects / Q000502:physiology; D013851:Thinness / Q000378:metabolism* / Q000503:physiopathology; D014662:Vasoconstrictor Agents / Q000494:pharmacology; D014665:Vasodilator Agents / Q000494:pharmacology
chemical_list: D014662:Vasoconstrictor Agents; D014665:Vasodilator Agents; D000804:Angiotensin II; D007545:Isoproterenol; D010100:Oxygen