The WNT inhibitor Dickkopf 1 and bone morphogenetic protein 4 rescue adipogenesis in hypertrophic obesity in humans.
The WNT inhibitor Dickkopf 1 and bone morphogenetic protein 4 rescue adipogenesis in hypertrophic obesity in humans.
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作者：
Gustafson B;Smith U
以脂肪细胞不适当扩张为特征的超重（肥大性肥胖）与代谢综合征相关，并且是由不能募集和分化新的前体细胞引起的。我们研究了骨形态发生蛋白4（BMP 4）和WNT活化在调节人脂肪细胞分化中的作用。首先去除分化簇（CD）14+/45+和CD 31+细胞，然后用/不用不同的WNT抑制剂和/或BMP 4分化人皮下活检样本的剩余基质血管细胞。WNT的抑制和Dickkopf 1（DKK 1）的诱导是前体细胞经历良好分化的标志。DKK 1的加入抑制WNT活化并促进低分化程度细胞的脂肪形成。DKK 1通过与Kremen/LDL受体相关蛋白受体结合抑制细胞WNT活化的积极作用，在分泌型WNT配体抑制剂中未观察到。BMP 4增加分化，并且在DKK 1存在下BMP 4产生累加效应。在分化和定型之间存在明显的相互作用，因为在分化的脂肪细胞中BMP 4表达增加，并且添加BMP 4抑制剂Noggin减少了前体细胞分化。因此，分化的人脂肪细胞可以通过内源性BMP 4活化促进脂肪形成，并且肥大性肥胖中受损的脂肪形成主要是由于不能抑制典型WNT和诱导DKK 1。
Overweight characterized by inappropriate expansion of adipose cells (hypertrophic obesity) is associated with the metabolic syndrome and is caused by an inability to recruit and differentiate new precursor cells. We examined the role of bone morphogenetic protein 4 (BMP4) and WNT activation in the regulation of human adipose cell differentiation. Cluster of differentiation (CD)14+/45+ and CD31+ cells were first removed before the remaining stromal vascular cells of human subcutaneous biopsy specimens were differentiated with/without different WNT inhibitors and/or BMP4. Inhibition of WNT and induction of Dickkopf 1 (DKK1) were markers of precursor cells undergoing excellent differentiation. The addition of DKK1 inhibited WNT activation and promoted adipogenesis in cells with a low degree of differentiation. The positive effect of DKK1, inhibiting cellular WNT activation by binding to the Kremen/LDL receptor–related protein receptors, was not seen with inhibitors of secreted WNT ligands. BMP4 increased differentiation, and BMP4 in the presence of DKK1 produced an additive effect. There was an apparent cross-talk between differentiation and commitment because BMP4 expression increased in differentiating adipocytes, and the addition of the BMP4 inhibitor, Noggin, reduced precursor cell differentiation. Thus, differentiated human adipose cells can promote adipogenesis via endogenous BMP4 activation, and the impaired adipogenesis in hypertrophic obesity is mainly due to an inability to suppress canonical WNT and to induce DKK1.
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影响因子：
30.8
作者：
通讯作者：
--
影响因子：
3.7
作者：
Schleinitz D;Klöting N;Böttcher Y;Wolf S;Dietrich K;Tönjes A;Breitfeld J;Enigk B;Halbritter J;Körner A;Schön MR;Jenkner J;Tseng YH;Lohmann T;Dressler M;Stumvoll M;Blüher M;Kovacs P
通讯作者：
Kovacs P
影响因子：
4.8
作者：
Gustafson, B;Smith, U
通讯作者：
Smith, U
影响因子：
4.3
作者：
Bowers, Robert R.;Lane, M. Daniel
通讯作者：
Lane, M. Daniel
影响因子：
7.7
作者：
Böttcher Y;Unbehauen H;Klöting N;Ruschke K;Körner A;Schleinitz D;Tönjes A;Enigk B;Wolf S;Dietrich K;Koriath M;Scholz GH;Tseng YH;Dietrich A;Schön MR;Kiess W;Stumvoll M;Blüher M;Kovacs P
通讯作者：
Kovacs P