Regulation of the fibrosis and angiogenesis promoter SPARC/osteonectin in human adipose tissue by weight change, leptin, insulin, and glucose.
Regulation of the fibrosis and angiogenesis promoter SPARC/osteonectin in human adipose tissue by weight change, leptin, insulin, and glucose.
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DOI：
10.2337/db09-0211
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发表时间：
2009-08
期刊：
影响因子：
7.7
通讯作者：
Wilding JP
中科院分区：
文献类型：
--
作者：
Kos K;Wong S;Tan B;Gummesson A;Jernas M;Franck N;Kerrigan D;Nystrom FH;Carlsson LM;Randeva HS;Pinkney JH;Wilding JP
基质细胞分泌蛋白，酸性和富含半胱氨酸（SPARC），最初发现于骨作为骨连接蛋白，是胶原沉积和促进纤维化的中介。脂肪组织胶原蛋白最近被发现与代谢失调有关。因此，我们验证了人类脂肪组织中的SPARC受葡萄糖代谢和脂肪因子影响的假设。对接受减肥手术的病态肥胖非糖尿病患者和瘦肉对照组进行血清和脂肪组织活检，分析代谢标志物、SPARC和各种细胞因子（RT-PCR）。此外，24名肥胖受试者接受了1883千焦（450千卡）/天的极低热量饮食，持续16周，并进行了一系列皮下腹部脂肪组织（SCAT）活检（体重减轻：28±3.7 kg）。另外6名瘦的受试者进行了为期4周的以快餐为基础的高营养饮食（体重增加：7.2±1.6 kg）。最后，用重组瘦素、胰岛素和葡萄糖培养内脏脂肪组织外植体，并通过Western blot检测SPARC mRNA和蛋白的表达。SPARC在人体脂肪组织中的表达与脂肪量相关，在SCAT中表达更高。极低热量饮食引起的体重减轻使快餐饮食后体重增加的受试者脂肪组织中的SPARC表达降低了33%，增加了30%。SPARC表达与瘦素相关，独立于脂肪量，与体内平衡模型评估-胰岛素抵抗相关。体外实验表明，瘦素和胰岛素能剂量依赖性地增加内脏脂肪组织外植体中SPARC的产生，而葡萄糖则能降低SPARC蛋白。我们的数据表明，SPARC在皮下脂肪中主要表达，其在脂肪组织中的表达和分泌受脂肪量、瘦素、胰岛素和葡萄糖的影响。SPARC的纤维化作用可能导致肥胖的代谢失调。
Matricellular Secreted Protein, Acidic and Rich in Cysteine (SPARC), originally discovered in bone as osteonectin, is a mediator of collagen deposition and promotes fibrosis. Adipose tissue collagen has recently been found to be linked with metabolic dysregulation. Therefore, we tested the hypothesis that SPARC in human adipose tissue is influenced by glucose metabolism and adipokines. Serum and adipose tissue biopsies were obtained from morbidly obese nondiabetic subjects undergoing bariatric surgery and lean control subjects for analysis of metabolic markers, SPARC, and various cytokines (RT-PCR). Additionally, 24 obese subjects underwent a very-low-calorie diet of 1,883 kJ (450 kcal)/day for 16 weeks and serial subcutaneous-abdominal-adipose tissue (SCAT) biopsies (weight loss: 28 ± 3.7 kg). Another six lean subjects underwent fast-food–based hyperalimentation for 4 weeks (weight gain: 7.2 ± 1.6 kg). Finally, visceral adipose tissue explants were cultured with recombinant leptin, insulin, and glucose, and SPARC mRNA and protein expression determined by Western blot analyses. SPARC expression in human adipose tissue correlated with fat mass and was higher in SCAT. Weight loss induced by very-low-calorie diet lowered SPARC expression by 33% and increased by 30% in adipose tissue of subjects gaining weight after a fast-food diet. SPARC expression was correlated with leptin independent of fat mass and correlated with homeostasis model assessment–insulin resistance. In vitro experiments showed that leptin and insulin potently increased SPARC production dose dependently in visceral adipose tissue explants, while glucose decreased SPARC protein. Our data suggest that SPARC expression is predominant in subcutaneous fat and its expression and secretion in adipose tissue are influenced by fat mass, leptin, insulin, and glucose. The profibrotic effects of SPARC may contribute to metabolic dysregulation in obesity.
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影响因子：
24.5
作者：
Kechagias S;Ernersson A;Dahlqvist O;Lundberg P;Lindström T;Nystrom FH;Fast Food Study Group
通讯作者：
Fast Food Study Group
影响因子：
168.9
作者：
Renehan, Andrew G.;Tyson, Margaret;Zwahlen, Marcel
通讯作者：
Zwahlen, Marcel
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4.4
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Atsumi, Toshiya;Cho, You-Ree;Bucala, Richard
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Bucala, Richard
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5.8
作者：
Gummesson, Anders;Jernas, Margareta;Carlsson, Lena M. S.
通讯作者：
Carlsson, Lena M. S.
影响因子：
3.5
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Camino, Alejandra M.;Atorrasagasti, Catalina;Mazzolini, Guillermo
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Mazzolini, Guillermo