期刊
BIOCHEMICAL JOURNAL
卷 416, 期 -, 页码 161-177出版社
PORTLAND PRESS LTD
DOI: 10.1042/BJ20081240
关键词
adipokine; adipose tissue; C1q/TNF family; C1q/TNF-related protein (CTRP); diabetes; obesity
资金
- National Institutes of Health National Institute of Diabetes and Digestive and Kidney Diseases [R37 DK47618-19]
- National Institutes of Health K08 [HL077499-01]
- National Institutes of Health National Research Service Award [F32DK067835]
- NATIONAL HEART, LUNG, AND BLOOD INSTITUTE [K08HL077499] Funding Source: NIH RePORTER
- NATIONAL INSTITUTE OF DIABETES AND DIGESTIVE AND KIDNEY DISEASES [R37DK047618, R01DK047618, F32DK067835] Funding Source: NIH RePORTER
The insulin-sensitizing hormone, adiponectin, belongs to the expanding Clq/TNF (tumour necrosis factor) family of proteins. We recently identified a family of adiponectin paralogues designated as CTRP ((C) under bar lq/(T) under bar NF-(r) under bar elated (p) under bar rotein) 1-7, and in the present study describe CTRP10. In the present Study, we show that CTRP1, CTRP2, CTRP3, CTRP5 and CTRP7 transcripts are expressed predominantly by adipose tissue. In contrast, placenta and eye expressed the highest levels of CTRP6 and CTRP10 transcripts respectively. Expression levels of CTRP1, CTRP2, CTRP3, CTRP6 and CTRP7 transcripts are up-regulated in 8-week-old obese (ob/ob) in ice relative to lean controls. Treatment of mice with a PPAR-gamma (peroxisome-proliferator-activated receptor-gamma) agonist, rosiglitazone, increased the expression of CTRP1 and decreased CTRP6 transcript levels. All CTRPs are secreted glycoproteins when expressed in mammalian cells. CTRP1, CTRP2, CTRP3, CTRP5 and CTRP6 circulate in the blood and are potential endocrine hormones; their serum levels vary according to the sex and genetic background of mice. Importantly, serum levels of CTRP1 and CTRP6 are increased in adiponectin-null mice. Like adiponectin, all secreted CTRP proteins form trimers its their basic structural units. CTRP3, CTRP5, CTRP6 and CTRP10 trimers are further assembled into higher-order oligorneric complexes via disulfide bonding mediated by their N-terminal cysteine residues. Besides forming homo-oligomners, CTRP1/CTRP6, CTRP2/CTRP7 and adiponectin/CTRP2 are secreted its heterotrimers, thus providing a mechanism to potentially generate functionally distinct ligands. Functional characterization of one such family member, CTRP1, showed that it specifically activates Akt and p44/42-MAPK (mitogen-activated protein kinase) signalling pathways in differentiated mouse myotubes. Moreover, injection of recombinant CTRP I into mice significantly reduced their serum glucose levels. Thus at least CTRP1 may be considered a novel adipokine. In summary, these molecular, biochemical and functional data provide an important framework to further address the physiological functions and mechanisms of the action of this family of secreted glycoproteins in normal and disease states.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据