DEVELOPMENTAL AND NUTRITIONAL CHANGES OF OB AND PPAR-GAMMA-2 GENE-EXPRESSION IN RAT WHITE ADIPOSE-TISSUE

The ob gene encodes leptin, a hormone which induces satiety and increa ses energy expenditure. The peroxisome proliferator activated receptor gamma 2 isoform (PPAR gamma 2) gene encodes a transcription factor wh ich controls adipocyte differentiation and expression of fat-specific genes. We have studied the regulation of these two genes in white adip ose tissue (WAT) during the suckling-weaning transition. Suckling rats ingest a high-fat diet (milk). Fat-pad weight barely varied during th e last week of suckling. ob mRNA levels, which were very low in 15-day -old rats, rose similar to 6-fold until weaning. at 21 days. When the rats were weaned on to a standard (high-carbohydrate) laboratory chow, epididymal WAT enlarged similar to 7-fold, and ob mRNA kept increasin g progressively and doubled between 21 and 30 days. This evolution con trasted with that of fatty acid synthase (FAS) mRNA, which increased s harply, but only after weaning. To distinguish between the influence o f developmental and nutritional factors on ob expression, a group of r ats was weaned on to a high-fat diet. This prevented the rise in glyca emia and insulinaemia and the decrease in plasma non-esterified fatty acids which otherwise occurred at weaning. This also resulted in a sli ght (10-15 %) decrease in food intake and body weight gain. Under this high-fat diet, the rise of ob mRNA in WAT was augmented (3.7-foId in 30- versus 21-day-old pups), whereas the normal rise in FAS mRNA lever s was attenuated. Fat-pad weights and adipocyte cell size and number w ere roughly similar in high-carbohydrate- and high-fat-weaned pups. mR NA levels of PPAR gamma 2, like those of ab, were low in the WAT of 15 -day-old suckling pups, doubled at 21 days, and reached a maximum as s oon as 23 days. This evolution further differed from that of ob mRNA i n not being influenced by diet composition. In conclusion, ob expressi on markedly increases during the suckling-weaning transition, and this effect is accentuated by a high-fat diet. Qualitative nutritional cha nges in ob mRNA were correlated with neither acute changes in adipose- tissue mass, nor cell size/number, nor variations in insulinaemia. PPA R gamma 2 also increased during suckling, but rapidly reached a platea u after weaning and no longer changed thereafter. Unlike ob, PPAR gamm a 2 was not influenced by the diet composition.