title: Impaired preadipocyte differentiation into adipocytes in subcutaneous abdominal adipose of PCOS-like female rhesus monkeys.
abstract: Metabolic characteristics of polycystic ovary syndrome women and polycystic ovary syndrome-like, prenatally androgenized (PA) female monkeys worsen with age, with altered adipogenesis of sc abdominal adipose potentially contributing to age-related adverse effects on metabolism. This study examines whether adipocyte morphology and gene expression in sc abdominal adipose differ between late reproductive-aged PA female rhesus monkeys compared with age-matched controls (C). Subcutaneous abdominal adipose of both groups was obtained for histological imaging and mRNA determination of zinc finger protein 423 (Zfp423) as a marker of adipose stem cell commitment to preadipocytes, and CCAAT/enhancer binding protein (C/EBP)α/peroxisome proliferator-activated receptor (PPAR)δ as well as C/EBPα/PPARγ as respective markers of early- and late-stage differentiation of preadipocytes to adipocytes. In all females combined, serum testosterone (T) levels positively correlated with fasting serum levels of total free fatty acid (r(2) = 0.73, P < .002). PA females had a greater population of small adipocytes vs C (P < .001) in the presence of increased Zfp423 (P < .025 vs C females) and decreased C/EBPα (P < .003, vs C females) mRNA expression. Moreover, Zfp423 mRNA expression positively correlated with circulating total free fatty acid levels during iv glucose tolerance testing (P < .004, r(2) = 0.66), whereas C/EBPα mRNA expression negatively correlated with serum T levels (P < .02, r(2) = 0.43). Gene expression of PPARδ and PPARγ were comparable between groups (P = .723 and P = .18, respectively). Early-to-mid gestational T excess in female rhesus monkeys impairs adult preadipocyte differentiation to adipocytes in sc abdominal adipose and may constrain the ability of this adipose depot to safely store fat with age.
authors.affiliation: Departments of Obstetrics and Gynecology (E.K., G.D.C., P.A., V.M., D.A.D.) and Medicine Statistics Core (T.G., D.E.), David Geffen School of Medicine at University of California, Los Angeles, Los Angeles, California 90095-1740; and Department of Obstetrics and Gynecology and Wisconsin National Primate Research Center (D.H.A.), University of Wisconsin, Madison, Wisconsin 53715.
authors.forename: Erica
authors.initials: E
authors.lastname: Keller
authors.forename: Gregorio D
authors.initials: GD
authors.lastname: Chazenbalk
authors.forename: Paul
authors.initials: P
authors.lastname: Aguilera
authors.forename: Vanessa
authors.initials: V
authors.lastname: Madrigal
authors.forename: Tristan
authors.initials: T
authors.lastname: Grogan
authors.forename: David
authors.initials: D
authors.lastname: Elashoff
authors.forename: Daniel A
authors.initials: DA
authors.lastname: Dumesic
authors.forename: David H
authors.initials: DH
authors.lastname: Abbott
mesh_terms: D017667:Adipocytes / Q000378:metabolism* / Q000473:pathology; D050156:Adipogenesis / Q000235:genetics; D000728:Androgens / Q000378:metabolism; D000818:Animals; D022763:CCAAT-Enhancer-Binding Protein-alpha / Q000235:genetics; D002454:Cell Differentiation / Q000235:genetics*; D005260:Female; D015870:Gene Expression; D006801:Humans; D008253:Macaca mulatta; D047494:PPAR delta / Q000235:genetics; D047495:PPAR gamma / Q000235:genetics; D011085:Polycystic Ovary Syndrome / Q000097:blood / Q000235:genetics* / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D050507:Subcutaneous Fat, Abdominal / Q000378:metabolism* / Q000473:pathology; D013739:Testosterone / Q000097:blood; D014157:Transcription Factors / Q000235:genetics; D016335:Zinc Fingers / Q000235:genetics
chemical_list: D000728:Androgens; D022763:CCAAT-Enhancer-Binding Protein-alpha; D047494:PPAR delta; D047495:PPAR gamma; D014157:Transcription Factors; D013739:Testosterone
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