Altered Transition of Adipocyte Stem Cell Commitment to Early Preadipocyte Differentiation in Subcutaneous Abdominal Adipose Tissue of Adult, PCOS-like Female Rhesus Monkeys

Program: Abstracts - Orals, Featured Poster Presentations, and Posters
Session: MON 548-560-Hyperandrogenic Disorders
Basic/Clinical
Monday, June 17, 2013: 1:45 PM-3:45 PM
Expo Halls ABC (Moscone Center)

Poster Board MON-555
Gregorio Daniel Chazenbalk1, Paul Aguilera1, Erica Keller1, Daniel Anthony Dumesic1 and David Howard Abbott*2
1University of California, Los Angeles, Los Angeles, CA, 2Univ of WI-Natl Primate Rsch C, Madison, WI
Metabolic phenotypes worsen with increasing age in both PCOS women and PCOS-like monkeys. Fetal testosterone (T)-exposed PCOS-like female monkeys are not only hyperlipidemic, but may also exhibit changes in adipogenic function and gene expression in subcutaneous (SC) abdominal adipose tissue that contribute to their age-pronounced metabolic dysfunction. The present study examines whether adipocyte morphology and gene expression of SC abdominal adipose differ between peri-menopausal early gestation T-exposed (T: n=6, 25.8±0.8 yr; mean±SEM) female rhesus monkeys compared to control animals (C: n=6) of comparable age (24.5±0.9 yr) and body mass index (BMI, C: 41.9±2.3; T: 38.1±2.9, kg/m2).

Methods: For cell sizing studies, ~0.5g frozen SC abdominal adipose was embedded in OCT, cut into 10μm sections, stained with H&E following standard protocols, and digitally imaged. mRNA gene expression, determined by qRT-PCR and expressed as Delta Ct values, included adipogenic genes Zfp423; C/EBPα and PPARδ; and PPARλ as markers of adipocyte stem cell commitment to preadipocytes, early-stage preadipocyte differentiation, and late-stage preadipocyte progression, respectively.

Results: Adipocyte area (AA), adipocyte circumference (AC) and the AA/AC ratio were similar between female groups. In T-exposed vs. C females, Zfp423 mRNA expression was increased (p<0.025), while C/EBPα mRNA expression was reciprocally diminished (p<0.003); PPARδ and PPARλ mRNA expression was comparable between female groups. In a subset of C (n=3) and T-exposed (n=5) females with similar volume of SC abdominal adipose by female group, a positive correlation was found between Zfp423 mRNA expression and area-under-the-curve total free fatty acids during an intravenous glucose tolerance test (p<0.008, r2=0.66, all females combined). Adipogenic gene expression with these selected markers was not associated with adipocyte morphology, glucoregulatory parameters, or animal BMI or age.

Conclusion: Early gestation T exposure may perturb SC abdominal adipogenesis during transition of adipocyte stem cell commitment to early preadipocyte differentiation, thereby constraining SC abdominal lipid storage as a mechanism of promoting lipotoxicity in PCOS women as they age.

Nothing to Disclose: GDC, PA, EK, DAD, DHA

*Please take note of The Endocrine Society's News Embargo Policy at http://www.endo-society.org/endo2013/media.cfm

Sources of Research Support: NIH grant HD044405 to A. Dunaif;  Department of OB/GYN at UCLA award.