Identification of cathepsin K as a novel marker of adiposity in white adipose tissue
Identification of cathepsin K as a novel marker of adiposity in white adipose tissue
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DOI：
10.1002/jcp.10253
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发表时间：
2003-05-01
影响因子：
5.6
通讯作者：
Maffei, M
中科院分区：
文献类型：
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作者：
Chiellini, C;Costa, M;Maffei, M
在肥胖症中，脂肪细胞经历与其基因表达谱改变相关的显著形态学和分子变化。为了鉴定肥胖db/db小鼠与野生型（wt）小鼠相比在白色脂肪组织（WAT）中差异调节的基因，我们利用RNA指纹法。在我们鉴定的52个候选者中，我们在这里集中于组织蛋白酶K（ctsk），一种半胱氨酸蛋白酶，其主要定位于溶酶体中并参与骨细胞外基质降解。在db/db小鼠中，WAT ctsk mRNA升高5.9倍，Mitt和TFE 3（分别为2倍和3.3倍），这两种转录因子参与破骨细胞中的ctsk诱导。此外，WAT ctsk mRNA水平在其他肥胖模型中增加，包括Ay，fat和tubby（分别为2.8，3.2和4.9倍），并在体重减轻的小鼠中降低。尽管ctsk转录本广泛分布，但我们证明肥胖相关的增加是脂肪细胞特有的。此外，体外实验证明，ctsk转录物的丰度在建立的前脂肪细胞3 T3-F442 A细胞系的脂肪转化后增加。此外，我们还检测了21名瘦型和肥胖型男性受试者脂肪组织中ctsk基因的表达，并发现ctsk基因的表达与BMI显著相关（r = 0.54，P = 0.012）与血浆瘦素水平（r = 0.54，P = 0.015）。总之，肥胖db/db小鼠的WAT表现出与野生型小鼠不同的表达谱，组织蛋白酶K可以被认为是肥胖症的新标志物和抑制脂肪量生长的靶点。J.细胞。195：309-321，2003。(C)2003 Wiley-Liss，Inc.
In obesity, adipocytes undergo dramatic morphological and molecular changes associated with alterations in their gene expression profile. To identify genes differentially modulated in white adipose tissue (WAT) of obese db/db mice compared to wild type (wt) mice, we utilized RNA fingerprinting. Among the 52 candidates that we identified, we focused here on cathepsin K (ctsk), a cysteine protease, prevalently localized in lysosomes and involved in bone extracellular matrix degradation. In db/db mice, WAT ctsk mRNA was elevated 5.9-fold, as were Mitt and TFE3 (2- and 3.3-fold respectively), two transcription factors involved in ctsk induction in osteoclasts. Moreover, the level of WAT ctsk mRNA was increased in other obese models including Ay, fat, and tubby (2.8-, 3.2-, and 4.9-fold respectively) and decreased in mice undergoing weight loss. Despite the ubiquitous distribution of the ctsk transcript, we demonstrated that the obesity related increase is specific to the adipocytes. Further, in vitro experiments proved that the abundance of ctsk transcript increases upon adipose conversion of the established cell line of preadipocytes 3T3-F442A. In addition, ctsk gene expression was examined in adipose tissue of 21 lean and obese male subjects and significant correlations with BMI (r = 0.54, P = 0.012) and plasma leptin levels (r = 0.54, P = 0.015) were found. In conclusion, the WAT of obese db/db mice exhibits a different expression profile from that of the wt mice, and cathepsin K can be considered a novel marker of obesity and a target for the inhibition of adipose mass growth. J. Cell. Physiol. 195: 309-321, 2003. (C) 2003 Wiley-Liss, Inc.