title: Prostaglandin (PG) F2 alpha synthesis in human subcutaneous and omental adipose tissue: modulation by inflammatory cytokines and role of the human aldose reductase AKR1B1.
abstract: BACKGROUND
  PGF2α may be involved in the regulation of adipose tissue function.
  
  
  OBJECTIVE
  1) To examine PGF2α release by primary preadipocytes, mature adipocytes and whole tissue explants from the subcutaneous and omental fat compartments; 2) To assess which PGF synthase is the most relevant in human adipose tissue.
  
  
  METHODS
  Fat samples were obtained by surgery in women. PGF2α release by preadipocytes, adipocytes and explants under stimulation by TNF-α, IL-1β or both was measured. Messenger RNA expression levels of AKR1B1 and AKR1C3 were measured by RT-PCR in whole adipose tissue and cytokine-treated preadipocytes. The effect of AKR1B1 inhibitor ponalrestat on PGF2α synthesis was investigated.
  
  
  RESULTS
  PGF2α release was significantly induced in response to cytokines compared to control in omental (p = 0.01) and to a lesser extent in subcutaneous preadipocytes (p = 0.02). Messenger RNA of COX-2 was significantly higher in omental compared to subcutaneous preadipocytes in response to combined TNF-α and IL-1β (p = 0.01). Inflammatory cytokines increased AKR1B1 mRNA expression and protein levels (p≤0.05), but failed to increase expression levels of AKR1C3 in cultured preadipocytes. Accordingly, ponalrestat blunted PGF2α synthesis by preadipocytes in basal and stimulated conditions (p≤0.05). Women with the highest PGF2α release by omental adipocytes had a higher BMI (p = 0.05), waist circumference (p≤0.05) and HOMAir index (p≤0.005) as well as higher mRNA expression of AKR1B1 in omental (p<0.10) and subcutaneous (p≤0.05) adipose tissue compared to women with low omental adipocytes PGF2α release. Positive correlations were observed between mRNA expression of AKR1B1 in both compartments and BMI, waist circumference as well as HOMAir index (p≤0.05 for all).
  
  
  CONCLUSIONS
  PGF2α release by omental mature adipocytes is increased in abdominally obese women. Moreover, COX-2 expression and PGF2α release is particularly responsive to inflammatory stimulation in omental preadipocytes. Yet, blockade of PGF synthase AKR1B1 inhibits most of the PGF2α release.
authors.affiliation: Endocrinology and Nephrology, Laval University Medical Center, Quebec City, Canada; Department of Nutrition, Laval University, Quebec City, Canada.
authors.forename: Andréanne
authors.initials: A
authors.lastname: Michaud
authors.affiliation: Reproduction and Biology, Laval University Medical Center, Quebec City, Canada.
authors.forename: Nicolas
authors.initials: N
authors.lastname: Lacroix-Pépin
authors.affiliation: Endocrinology and Nephrology, Laval University Medical Center, Quebec City, Canada.
authors.forename: Mélissa
authors.initials: M
authors.lastname: Pelletier
authors.affiliation: Department of Nutrition, Laval University, Quebec City, Canada.
authors.forename: Alain
authors.initials: A
authors.lastname: Veilleux
authors.affiliation: Gynecology Unit, Laval University Medical Center, Quebec City, Canada.
authors.forename: Suzanne
authors.initials: S
authors.lastname: Noël
authors.affiliation: Gynecology Unit, Laval University Medical Center, Quebec City, Canada.
authors.forename: Céline
authors.initials: C
authors.lastname: Bouchard
authors.affiliation: Department of Surgery, Quebec Cardiology and Pulmonology Institute, Quebec City, Canada.
authors.forename: Picard
authors.initials: P
authors.lastname: Marceau
authors.affiliation: Reproduction and Biology, Laval University Medical Center, Quebec City, Canada.
authors.forename: Michel A
authors.initials: MA
authors.lastname: Fortier
authors.affiliation: Endocrinology and Nephrology, Laval University Medical Center, Quebec City, Canada; Department of Nutrition, Laval University, Quebec City, Canada.
authors.forename: André
authors.initials: A
authors.lastname: Tchernof
mesh_terms: D017667:Adipocytes / Q000187:drug effects / Q000378:metabolism; D000328:Adult; D000449:Aldehyde Reductase / Q000037:antagonists & inhibitors / Q000378:metabolism*; D051546:Cyclooxygenase 2 / Q000378:metabolism; D016207:Cytokines / Q000378:metabolism*; D015237:Dinoprost / Q000096:biosynthesis* / Q000378:metabolism*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005260:Female; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects; D005947:Glucose / Q000378:metabolism; D006706:Homeostasis / Q000187:drug effects; D006801:Humans; D007249:Inflammation / Q000378:metabolism; D008264:Macrophages / Q000166:cytology / Q000276:immunology; D008875:Middle Aged; D009765:Obesity / Q000378:metabolism / Q000473:pathology; D009852:Omentum / Q000166:cytology* / Q000473:pathology; D050151:Subcutaneous Fat / Q000187:drug effects / Q000378:metabolism*
chemical_list: D016207:Cytokines; D004791:Enzyme Inhibitors; D015237:Dinoprost; C484670:AKR1B1 protein, human; D000449:Aldehyde Reductase; D051546:Cyclooxygenase 2; D005947:Glucose