title: Adipose tissue has aberrant morphology and function in PCOS: enlarged adipocytes and low serum adiponectin, but not circulating sex steroids, are strongly associated with insulin resistance.
abstract: BACKGROUND
  Comprehensive characterization of the adipose tissue in women with polycystic ovary syndrome (PCOS), over a wide range of body mass indices (BMIs), is lacking. Mechanisms behind insulin resistance in PCOS are unclear.
  
  
  OBJECTIVE
  To characterize the adipose tissue of women with PCOS and controls matched pair-wise for age and BMI, and to identify factors, among adipose tissue characteristics and serum sex steroids, that are associated with insulin sensitivity in PCOS.
  
  
  METHODS
  Seventy-four PCOS women and 31 controls were included. BMI was 18-47 (PCOS) and 19-41 kg/m(2) (controls). Anthropometric variables, volumes of subcutaneous/visceral adipose tissue (magnetic resonance imaging; MRI), and insulin sensitivity (clamp) were investigated. Adipose tissue biopsies were obtained to determine adipocyte size, lipoprotein lipase (LPL) activity, and macrophage density. Circulating testosterone, free testosterone, free 17β-estradiol, SHBG, glycerol, adiponectin, and serum amyloid A were measured/calculated.
  
  
  RESULTS
  Comparison of 31 pairs revealed lower insulin sensitivity, hyperandrogenemia, and higher free 17β-estradiol in PCOS. Abdominal adipose tissue volumes/distribution did not differ in the groups, but PCOS women had higher waist-to-hip ratio, enlarged adipocytes, reduced adiponectin, and lower LPL activity. In regression analysis, adipocyte size, adiponectin, and waist circumference were the factors most strongly associated with insulin sensitivity in PCOS (R(2)=0.681, P < 0.001).
  
  
  CONCLUSIONS
  In PCOS, adipose tissue has aberrant morphology/function. Increased waist-to-hip ratio indicates abdominal/visceral fat accumulation, but this is not supported by MRI. Enlarged adipocytes and reduced serum adiponectin, together with a large waistline, rather than androgen excess, may be central factors in the pathogenesis/maintenance of insulin resistance in PCOS.
authors.affiliation: Institute of Neuroscience and Physiology, Department of Physiology, Sahlgrenska Academy, University of Gothenburg, SE-405 30 Gothenburg, Sweden.
authors.forename: Louise
authors.initials: L
authors.lastname: Mannerås-Holm
authors.forename: Henrik
authors.initials: H
authors.lastname: Leonhardt
authors.forename: Joel
authors.initials: J
authors.lastname: Kullberg
authors.forename: Eva
authors.initials: E
authors.lastname: Jennische
authors.forename: Anders
authors.initials: A
authors.lastname: Odén
authors.forename: Göran
authors.initials: G
authors.lastname: Holm
authors.forename: Mikael
authors.initials: M
authors.lastname: Hellström
authors.forename: Lars
authors.initials: L
authors.lastname: Lönn
authors.forename: Gunilla
authors.initials: G
authors.lastname: Olivecrona
authors.forename: Elisabet
authors.initials: E
authors.lastname: Stener-Victorin
authors.forename: Malin
authors.initials: M
authors.lastname: Lönn
mesh_terms: D017667:Adipocytes / Q000473:pathology*; D052242:Adiponectin / Q000097:blood*; D000273:Adipose Tissue / Q000473:pathology*; D000328:Adult; D000682:Amyloid / Q000097:blood; D001827:Body Height / Q000502:physiology; D015992:Body Mass Index; D001835:Body Weight / Q000502:physiology; D048429:Cell Size; D005260:Female; D005990:Glycerol / Q000097:blood; D012739:Gonadal Steroid Hormones / Q000097:blood*; D006801:Humans; D007150:Immunohistochemistry; D007333:Insulin Resistance / Q000502:physiology*; D008071:Lipoprotein Lipase / Q000378:metabolism; D008264:Macrophages / Q000473:pathology; D011085:Polycystic Ovary Syndrome / Q000473:pathology*; D012738:Sex Hormone-Binding Globulin / Q000378:metabolism; D055105:Waist Circumference; D049629:Waist-Hip Ratio
chemical_list: D052242:Adiponectin; D000682:Amyloid; D012739:Gonadal Steroid Hormones; D012738:Sex Hormone-Binding Globulin; D008071:Lipoprotein Lipase; D005990:Glycerol