Association Between Precursor Cells Commitment and Adipose Tissue Mass Expansion in Hypercorticosteronemic Obese Rats over Development.

ZUBIRIA G; SPINEDI E; GIOVAMBATTISTA A

Chicago

Congreso; ICE/ENDO 2014; 2014

ESO

Adipose tissue (AT) overexpansion is one of the main features of obesity. This could result from either AT hyperplasia, adipocyte hypertrophy or both. This last has been proposed to have a prevalent contribution in advanced obesity states. We studied several features indicative for AT mass expansion in both, L-monosodium glutamate (MSG)-treated (neonatally) and normal littermate (CTR) male rats over development (pre-pubertal and adult ages). Retroperitoneal AT (RPAT) pads were aseptically dissected, weighted and, thereafter, mature adipocytes and Stromal Vascular Fraction (SVF) cells were isolated. RPAT adipocyte diameter was determined (image analyses) and adipocyte size frequency histograms were built. Adipose precursor cell (APC) number was counted by the flow cytometry immuno-staining strategy (CD34+/CD31-/CD45-). Specific adipocyte determination (PPAR-g2 and Zfp 423) and, pro- (MR, GR) and anti- (Pref-1, Wnt10b) adipogenic gene markers were quantified in SVF cells (qPCR Real Time). MSG rats showed increased RPAT mass and, the circulating levels of corticosterone and leptin (P < 0.05 vs. CTR values) at both ages examined. Data indicated that RPAT pads from 30 day-old MSG rats displayed only one population of large adipocytes after comparison with cells from CTR littermates. Conversely, RPAT pads from adult 60 day-old MSG rats showed two (vs. one adipocyte population in CTR) different populations of adipocytes: one small, presumably  new, and the other enlarged (P < 0.05). APC number in SVF cells was similar in both groups, regardless of the age examined.  Zfp423 and PPARg2 mRNA levels were higher (vs. CTR; P < 0.05) in SVF cells from pre-pubertal MSG rats; however, at adult age these markers were lower in MSG than CTR SVF cells. Finally, 30 day-old MSG SVF cells displayed increased pro-adipogenic (MR) and decreased anti-adipogenic (Pref-1/ Wnt10b) mRNAs levels (P < 0.05 vs. CTR); conversely, SVF cells from adult MSG rats showed a completely opposite expression pattern of these genes. Our data demonstrate that while MSG RPAT mass expansion in pre-pubertal rats is due to cell hypertrophy, in adult rats results from both AT hyperplasia and cell enlargement. This study suggests that an active adipogenic process takes place on different ages in MSG rats over development. The degree of commitment in MSG RPAT SVF cells from rats on different ages could be, at least in part, responsible for the different pattern of AT mass expansion.