Rousseau V, Becker D J, Ongemba L N, Rahier J, Henquin J C, Brichard S M
Endocrinology and Metabolism Unit, Faculty of Medicine, University of Louvain, Brussels, Belgium.
Biochem J. 1997 Jan 15;321 ( Pt 2)(Pt 2):451-6. doi: 10.1042/bj3210451.
The ob gene encodes leptin, a hormone which induces satiety and increases energy expenditure. The peroxisome proliferator-activated receptor gamma 2 isoform (PPAR gamma 2) gene encodes a transcription factor which controls adipocyte differentiation and expression of fat-specific genes. We have studied the regulation of these two genes in white adipose tissue (WAT) during the suckling-weaning transition. Suckling rats ingest a high-fat diet (milk). Fat-pad weight barely varied during the last week of suckling. ob mRNA levels, which were very low in 15-day-old rats, rose approximately 6-fold until weaning at 21 days. When the rats were weaned on to a standard (high-carbohydrate) laboratory chow, epididymal WAT enlarged approximately 7-fold, and ob mRNA kept increasing progressively and doubled between 21 and 30 days. This evolution contrasted with that of fatty acid synthase (FAS) mRNA, which increased sharply, but only after weaning. To distinguish between the influence of developmental and nutritional factors on ob expression, a group of rats was weaned on to a high-fat diet. This prevented the rise in glycaemia and insulinaemia and the decrease in plasma non-esterified fatty acids which otherwise occurred at weaning. This also resulted in a slight (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-fold in 30- versus 21-day-old pups), whereas the normal rise in FAS mRNA levels was attenuated. Fat-pad weights and adipocyte cell size and number were roughly similar in high-carbohydrate- and high-fat-weaned pups. mRNA levels of PPAR gamma 2, like those of ob, were low in the WAT of 15-day-old suckling pups, doubled at 21 days, and reached a maximum as soon as 23 days. This evolution further differed from that of ob mRNA in not being influenced by diet composition. In conclusion, ob expression markedly increases during the suckling-weaning transition, and this effect is accentuated by a high-fat diet. Qualitative nutritional changes in ob mRNA were correlated with neither acute changes in adipose-tissue mass, nor cell size/number, nor variations in insulinaemia. PPAR gamma 2 also increased during suckling, but rapidly reached a plateau after weaning and no longer changed thereafter. Unlike ob, PPAR gamma 2 was not influenced by the diet composition.
ob基因编码瘦素，一种可诱导饱腹感并增加能量消耗的激素。过氧化物酶体增殖物激活受体γ2亚型（PPARγ2）基因编码一种转录因子，该转录因子控制脂肪细胞分化及脂肪特异性基因的表达。我们研究了在哺乳-断奶过渡期白色脂肪组织（WAT）中这两个基因的调控情况。哺乳大鼠摄入高脂饮食（乳汁）。在哺乳的最后一周，脂肪垫重量几乎没有变化。ob mRNA水平在15日龄大鼠中非常低，到21日龄断奶时上升了约6倍。当大鼠断奶后改为标准（高碳水化合物）实验室饲料时，附睾WAT增大了约7倍，ob mRNA持续逐渐增加，并在21至30天之间翻倍。这种变化与脂肪酸合酶（FAS）mRNA的变化形成对比，FAS mRNA在断奶后才急剧增加。为了区分发育因素和营养因素对ob表达的影响，一组大鼠断奶后改为高脂饮食。这阻止了断奶时血糖和胰岛素血症的升高以及血浆非酯化脂肪酸的降低。这也导致食物摄入量和体重增加略有（10 - 15%）下降。在这种高脂饮食下，WAT中ob mRNA的升高增强（30日龄幼崽相对于21日龄幼崽升高3.7倍），而FAS mRNA水平的正常升高则减弱。高碳水化合物断奶和高脂断奶幼崽的脂肪垫重量、脂肪细胞大小和数量大致相似。PPARγ2的mRNA水平与ob的mRNA水平一样，在15日龄哺乳幼崽的WAT中较低，在21日龄时翻倍，并在23日龄时即达到最大值。这种变化与ob mRNA的变化进一步不同，不受饮食组成的影响。总之，ob表达在哺乳-断奶过渡期显著增加，高脂饮食会加剧这种影响。ob mRNA的定性营养变化与脂肪组织质量的急性变化、细胞大小/数量或胰岛素血症的变化均无关联。PPARγ2在哺乳期间也增加，但断奶后迅速达到平台期，此后不再变化。与ob不同，PPARγ2不受饮食组成的影响。
