title: Increased estrogen receptor β in adipose tissue is associated with increased intracellular and reduced circulating adiponectin protein levels in aged female rats.
abstract: BACKGROUND
  Obesity and associated metabolic and cardiovascular disease risk are correlated with reduced circulating adiponectin (APN) levels. Metabolic and cardiovascular disease risk is also increased after menopause and may be linked to disturbances in estrogen receptor (ER) signaling in adipose.
  
  
  OBJECTIVE
  We hypothesized that age-associated estrogen (E(2))-deficiency alters the ERα/β ratio in adipose tissue and increases risk for metabolic disease via APN-ac activated mechanisms.
  
  
  METHODS
  Visceral adipose was isolated from adult (6 months) and aged (24 months) female Fisher 344 rats (n = 5-6/group) with ovaries intact or removed by surgical ovariectomy (OVX) and subjected to western blotting.
  
  
  RESULTS
  Notably, weight was greatest in aged OVX rats (P < 0.01) and associated with a 2-fold increase in ERβ protein versus adult intact rats (P < 0.001). ER levels were increased in aged OVX versus adult OVX rats. Intra-adipocyte APN was also increased in aged OVX rats versus all groups (P < 0.01), whereas circulating APN levels decreased in aged OVX versus adult OVX rats (P < 0.05). Endoplasmic reticulum protein of 44 kDa (Erp44) levels remained the same (P = 0.09). Adiponectin receptor-1 (AdipoR1) and peroxisome proliferator-activated receptor-α (PPAR-α) were also unchanged. AdipoR2, PPAR-γ, and phosphorylated adenosine monophosphate-dependant kinase (pAMPK) to total AMPK ratio all decreased with age (P < 0.05).
  
  
  CONCLUSIONS
  Collectively, these data suggested that age-associated increases in ERβ paired with decreased PPAR-γ levels might predispose E(2)-deficient postmenopausal women for increased adiposity and associated metabolic and cardiovascular disease risk. Reduced circulating APN and AdipoR2 levels might contribute to age and E(2)-deficiency linked disease progression.
authors.affiliation: Intercollege Program in Physiology, The Pennsylvania State University, University Park, Pennsylvania 16802, USA.
authors.forename: Nanette J
authors.initials: NJ
authors.lastname: Tomicek
authors.forename: Timothy S
authors.initials: TS
authors.lastname: Lancaster
authors.forename: Donna H
authors.initials: DH
authors.lastname: Korzick
mesh_terms: D055372:AMP-Activated Protein Kinases / Q000378:metabolism; D052242:Adiponectin / Q000097:blood / Q000378:metabolism*; D000273:Adipose Tissue / Q000378:metabolism*; D000367:Age Factors; D000818:Animals; D001835:Body Weight; D047629:Estrogen Receptor beta / Q000378:metabolism*; D004967:Estrogens / Q000172:deficiency*; D005260:Female; D047908:Intracellular Signaling Peptides and Proteins / Q000378:metabolism; D010052:Ovariectomy; D047493:PPAR alpha / Q000378:metabolism; D047495:PPAR gamma / Q000378:metabolism; D051381:Rats; D054419:Receptors, Adiponectin / Q000378:metabolism
chemical_list: D052242:Adiponectin; C570523:Erp44 protein, rat; D047629:Estrogen Receptor beta; D004967:Estrogens; D047908:Intracellular Signaling Peptides and Proteins; D047493:PPAR alpha; D047495:PPAR gamma; D054419:Receptors, Adiponectin; C504339:adiponectin receptor 1, rat; C506573:adiponectin receptor 2, rat; D055372:AMP-Activated Protein Kinases