Tenomodulin promotes human adipocyte differentiation and beneficial visceral adipose tissue expansion.
Tenomodulin promotes human adipocyte differentiation and beneficial visceral adipose tissue expansion.
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DOI：
10.1038/ncomms10686
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发表时间：
2016-02-16
影响因子：
16.6
通讯作者：
Czech MP
中科院分区：
文献类型：
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作者：
Senol-Cosar O;Flach RJ;DiStefano M;Chawla A;Nicoloro S;Straubhaar J;Hardy OT;Noh HL;Kim JK;Wabitsch M;Scherer PE;Czech MP
脂肪组织中能量储存的适当调节对于维持胰岛素敏感性至关重要，而促进这一过程的分子尚未完全揭示。在这里，我们发现，与体重指数 (BMI) 相匹配的胰岛素抵抗个体与胰岛素敏感个体的脂肪组织中 II 型跨膜蛋白肌腱调节蛋白 (TNMD) 上调。在分化过程中，人前脂肪细胞中 TNMD 表达增加，而沉默 TNMD 则会阻碍脂肪生成。在高脂肪饮食喂养后，过度表达 Tnmd 的转基因小鼠的附睾白色脂肪组织 (eWAT) 质量增加，来自 Tnmd 转基因小鼠的前脂肪细胞显示出更大的增殖，与脂肪生成的增加一致。在 Tnmd 转基因小鼠中，eWAT 中的脂肪生成基因上调，棕色脂肪中的 Ucp1 也上调，而肝脏甘油三酯积累则减弱。尽管 eWAT 扩大，但转基因动物表现出改善的全身胰岛素敏感性、减少 eWAT 中的胶原沉积和炎症以及增加胰岛素对 Akt 磷酸化的刺激。我们的数据表明，TNMD 作为内脏脂肪组织的保护因子，可减轻肥胖患者的胰岛素抵抗。 内脏脂肪组织的扩张通常与胰岛素抵抗和代谢疾病有关。在这里，作者表明膜蛋白 TNMD 在胰岛素抵抗肥胖个体的内脏脂肪中上调，并通过增加脂肪生成促进健康的脂肪组织扩张。
Proper regulation of energy storage in adipose tissue is crucial for maintaining insulin sensitivity and molecules contributing to this process have not been fully revealed. Here we show that type II transmembrane protein tenomodulin (TNMD) is upregulated in adipose tissue of insulin-resistant versus insulin-sensitive individuals, who were matched for body mass index (BMI). TNMD expression increases in human preadipocytes during differentiation, whereas silencing TNMD blocks adipogenesis. Upon high-fat diet feeding, transgenic mice overexpressing Tnmd develop increased epididymal white adipose tissue (eWAT) mass, and preadipocytes derived from Tnmd transgenic mice display greater proliferation, consistent with elevated adipogenesis. In Tnmd transgenic mice, lipogenic genes are upregulated in eWAT, as is Ucp1 in brown fat, while liver triglyceride accumulation is attenuated. Despite expanded eWAT, transgenic animals display improved systemic insulin sensitivity, decreased collagen deposition and inflammation in eWAT, and increased insulin stimulation of Akt phosphorylation. Our data suggest that TNMD acts as a protective factor in visceral adipose tissue to alleviate insulin resistance in obesity. Expansion of visceral adipose tissue is usually associated with insulin resistance and metabolic disease. Here, the authors show that the membrane protein TNMD is upregulated in visceral fat of insulin resistant obese individuals and promotes healthy adipose tissue expansion through increasing adipogenesis.