Relationship between impaired adipogenesis of retroperitoneal adipose tissue and hypertrophic obesity: role of endogenous glucocorticoid excess

ZUBIRIA GUILLERMINA; VIDAL BRAVO, JUANA; SPINEDI, EDUARDO; GIOVAMBATTISTA , ANDRÉS

JOURNAL OF CELLULAR AND MOLECULAR MEDICINE (PRINT)

WILEY-BLACKWELL PUBLISHING, INC

Lugar: Londres; Año: 2014 vol. 8 p. 1549 - 1561

1582-1838

Although the pro-adipogenic effect of glucocorticoid (GC) on adipose tissue (AT) precursor cell differentiation is openly accepted, the effect ofchronically high peripheral levels of GC on AT mass expansion is not fully understood. In the present study, we aim to assess the in vitro adipogeniccapacity of AT precursor cells isolated from retroperitoneal (RP) AT pads of the hypercorticosteronaemic, adult neonatally treated monosodiumL-glutamate (MSG) male rat. To ascertain this issue, we explored the in vitro adipogenic process of stromal-vascular fraction (SVF)cells isolated from RPAT pads of 60-day-old MSG rats. The data recorded indicated that RPAT-SVF cells from hypercorticosteronaemic MSGrats, although displaying an enhanced proliferation capacity, differentiated slower than normal cells. This dysfunction was associated with areduction in key parameters indicative of precursor cell commitment, differentiation capacity and the percentage of fully differentiated adipocytes,with a retarded maturation process. The distorted adipogenic capacity was highly conditioned by RPAT-SVF cells displaying a low committedpopulation and both excessive and reduced expression of anti- (Pref-1 and Wnt-10b) and pro-adipogenic (mineralocorticoid receptor)signals respectively. Notably, the normalization of peripheral corticosterone levels in MSG rats, as a result of bilateral adrenalectomy combinedwith GC replacement therapy, fully prevented reduced RPAT precursor cell commitment and overall impaired adipogenesis. Our study stronglysupports that the impaired adipogenic process observed in the adult hypertrophic obese MSG male rat is a GC-dependent mechanism, thusexplaining the unhealthy RPAT expansion observed in human hypertrophic obese phenotypes, such as in the Cushing?s syndrome.