Dedifferentiation of fat cells improves the adipogenic and osteogenic capacity of obese human fat progenitor cells

Program: Abstracts - Orals, Featured Poster Presentations, and Posters
Session: SAT 649-659-Basic Mechanisms of Obesity
Saturday, June 15, 2013: 1:45 PM-3:45 PM
Expo Halls ABC (Moscone Center)

Poster Board SAT-657
Denise R. Cooper*1, Gay Carter2, James Watson2, Rekha Patel3, Abhishek Mather4, Michel M. Murr4, Paula Bickford4, Lisa J. Gould4 and Niketa A. Patel2
1James A. Haley VA Hospital, Tampa, FL, 2J.A. Haley VA Hospital, Tampa, FL, 3University of South Florida, Tampa, FL, 4University of South Florida
Obesity and osteoporosis, two disorders of body composition, are growing in high proportion worldwide, as major public health concerns. The effects of obesity on bone metabolism are not well defined, however, obesity and osteoporosis share several features including a common progenitor mesenchymal stem cell (MSC).  Whereas weight loss improves the adipogenic capacity of human adipose derived stem cells (ADSC) in obese subjects, it is unknown what may happen to the osteogenic capacity of stem cells with weight loss since there is a general positive effect of mechanical loading conferred by weight on bone formation.  Several lines of evidence suggest that obesity and bone metabolism are interrelated.  To study this, we derived subcutaneous ADSC from a female donor (45 yr, BMI 48, DM) and dedifferentiated fat (DFAT) cells by ceiling culture and hypoxia to a stem cell-like state from mature adipocytes of the same tissue depot (USF IRB#108360).  Phenotypic MSC surface markers indicated similar levels of CD105 (19% ADSC, 17.9% DFAT), CD34 negative (both), CD90 (98.5% ADSC, 99.4% DFAT), CD44 (87.8% ADSC, 89.1% DFAT), and CD117 (0.3% ADSC, 0.3% DFAT) determined by flow cytometry after passages 5-7.  When ADSC and DFAT cells were induced to differentiate into adipocytes for 14 days, 60% of DFAT cells accumulated oil red O, whereas only 30% of ADSC cells accumulated the dye.  Both cell types were exposed to osteogenic differentiation media for 2-4 weeks.  DFAT cells deposited calcium crystals (Alizarian red stain) at a faster rate than ADSC.   ADSC and DFAT cells expressed embryonic stem cell markers at varying levels.  DFAT cells expressed two-fold higher telomerase levels than ADSC.  Thus, the dedifferentiated fat cells mimic the effect of weight loss by improving the adipogenic capacity of stem cells.  The process also improved the osteogenic capacity of the DFAT cells. The data indicate that this unique model will allow for the dissection of the reprogramming steps that are similar to those seen in weight loss and allow for focus on cellular pathways such that new treatments can be tested in culture for obesity and osteoporosis.

Nothing to Disclose: DRC, GC, JW, RP, AM, MMM, PB, LJG, NAP

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Sources of Research Support: Supported by VA Merit Review to D.R.C.