RELATIVE RESISTANCE OF ADIPOCYTES FROM MASSIVELY OBESE PERSONS TO DEDIFFERENTIATION

Previous studies on the etiology of obesity have revealed that human a dipocytes have the ability to revert or dedifferentiate in culture to a morphology and replicative capacity similar to that of adipocyte pre cursors. To characterize some of the events of this process, we isolat ed adipocytes from the greater omentum of 61 morbidly obese and ten no rmal weight individuals with collagenase, and cultured them for 0, 4, and 7 days. In both lean and obese patients, sn-glycerol-3-phosphate d ehydrogenase specific activity decreased significantly after days 4 an d 7 compared to day 0. Dedifferentiation was also monitored by phase-c ontrast microscopy, which revealed that adipocytes from the lean had l ost appreciable lipid and had assumed an elongated contour more rapidl y than those from the obese. Reversion was also corroborated by revers e transcription-polymerase chain reaction, which indicated a decrease in the expression of sn-glycerol-3-phosphate dehydrogenase mRNA, and a n increase in actin and glyceraldehyde-3-phosphate dehydrogenase mRNA over the 7 days. Thus, this work has described some biochemical and mo lecular genetic characteristics of dedifferentiation. The relative res istance of adipocytes from morbidly obese patients to revert in cultur e may reflect the inordinately high propensity of fat cells in massive ly obese persons to preserve the differentiated, triacylglycerol-overf illed state.