Obesity reduces bone density associated with activation of PPARγ and suppression of Wnt/β-catenin in rapidly growing male rats.
Obesity reduces bone density associated with activation of PPARγ and suppression of Wnt/β-catenin in rapidly growing male rats.
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DOI：
10.1371/journal.pone.0013704
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发表时间：
2010-10-28
期刊：
影响因子：
3.7
通讯作者：
Ronis MJ
中科院分区：
文献类型：
--
作者：
Chen JR;Lazarenko OP;Wu X;Tong Y;Blackburn ML;Shankar K;Badger TM;Ronis MJ
众所周知，过度食用高脂肪饮食（HFD）会导致肥胖;然而，肥胖对出生后骨骼发育的影响尚未得到很好的研究。采用全肠内营养（TEN）对出生后第27天的雄性大鼠灌胃45%高脂饲料（HFD）4周以诱导肥胖。与饲喂含25%脂肪的TEN饲料（中脂肪饲料，MFD）或随意饲喂普通饲料（低脂饲料，LFD）的大鼠相比，脂肪量增加，体重增加匹配。HFD大鼠血清瘦素和总非酯化脂肪酸（NEFA）升高，与LFD喂养的动物相比，HFD大鼠的骨量也降低。这伴随着骨形成减少，但骨吸收增加。与LFD对照组相比，HFD大鼠的骨髓肥胖和成脂基因、PPARγ和aP 2的表达增加，而成骨细胞标志物骨钙素和Runx 2在骨中减少。基质细胞分化对HFD反应的转向源于骨中关键的经典Wnt信号分子β-catenin蛋白的下调和核PPARγ表达的相互上调。在一组体外研究中，使用用来自不同饮食的大鼠的血清处理的多能ST 2骨髓间充质基质细胞或使用通过GC-MS在来自HFD喂养的动物的大鼠血清中定量的NEFA的游离脂肪酸组成，我们能够概括我们的体内发现。这些观察结果有力地表明，从大鼠血清中增加NEFA的HFD喂养肥胖损害骨形成由于骨髓脂肪生成的刺激。肥胖对早期骨骼的这些影响可能导致峰值骨量的获得受损，因此增加了以后骨质疏松症的患病率。
It is well established that excessive consumption of a high fat diet (HFD) results in obesity; however, the consequences of obesity on postnatal skeletal development have not been well studied. Total enteral nutrition (TEN) was used to feed postnatal day 27 male rats intragastrically with a high 45% fat diet (HFD) for four weeks to induce obesity. Fat mass was increased compared to rats fed TEN diets containing 25% fat (medium fat diet, MFD) or a chow diet (low fat diet, LFD) fed ad libitum with matched body weight gains. Serum leptin and total non-esterified fatty acids (NEFA) were elevated in HFD rats, which also had reduced bone mass compared to LFD-fed animals. This was accompanied by decreases in bone formation, but increases in the bone resorption. Bone marrow adiposity and expression of adipogenic genes, PPARγ and aP2 were increased, whereas osteoblastogenic markers osteocalcin and Runx2 were decreased, in bone in HFD rats compared to LFD controls. The diversion of stromal cell differentiation in response to HFD stemmed from down-regulation of the key canonical Wnt signaling molecule β-catenin protein and reciprocal up-regulation of nuclear PPARγ expression in bone. In a set of in vitro studies using pluripotent ST2 bone marrow mesenchymal stromal cells treated with serum from rats on the different diets or using the free fatty acid composition of NEFA quantified in rat serum from HFD-fed animals by GC-MS, we were able to recapitulate our in vivo findings. These observations strongly suggest that increased NEFA in serum from rats made obese by HFD-feeding impaired bone formation due to stimulation of bone marrow adipogenesis. These effects of obesity on bone in early life may result in impaired attainment of peak bone mass and therefore increase the prevalence of osteoporosis later on in life.
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影响因子：
4.2
作者：
Kyung, Tae-Wook;Lee, Ji-Eun;Choi, Hye-Seon
通讯作者：
Choi, Hye-Seon
DOI：
10.1016/j.ajodo.2005.12.034
发表时间：
2007-08-01
影响因子：
3
作者：
Akridge, Matthew;Hilgers, Kelly K.;Kinane, Denis F.
通讯作者：
Kinane, Denis F.
影响因子：
6.2
作者：
Bielohuby, Maximilian;Matsuura, Maiko;Bidlingmaier, Martin
通讯作者：
Bidlingmaier, Martin
影响因子：
6.2
作者：
Parhami, F;Tintut, Y;Demer, LL
通讯作者：
Demer, LL
影响因子：
56.9
作者：
Hong, JH;Hwang, ES;Yaffe, MB
通讯作者：
Yaffe, MB