Loss of neuronatin promotes "browning" of primary mouse adipocytes while reducing Glut1-mediated glucose disposal.
Loss of neuronatin promotes "browning" of primary mouse adipocytes while reducing Glut1-mediated glucose disposal.
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DOI：
10.1152/ajpendo.00463.2012
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发表时间：
2013-04-15
期刊：
影响因子：
--
通讯作者：
Timmons JA
中科院分区：
文献类型：
--
作者：
Gburcik V;Cleasby ME;Timmons JA
白色脂肪组织不能适当地储存多余的代谢底物似乎是肥胖相关的2型糖尿病的基础。鼓励白色脂肪的“褐变”已被建议作为一种治疗策略，以帮助处理多余的储存脂质和改善由此产生的胰岛素抵抗。编码新型蛋白质脂质神经蛋白的DNA位点的遗传变异与肥胖有关，我们最近观察到，肥胖人群皮下脂肪组织中的神经蛋白表达减少。因此，为了进一步探索神经元蛋白的功能，我们在小鼠原代脂肪细胞培养中使用RNAi沉默其表达，并检测其对脂肪细胞表型的影响。我们发现，原代脂肪细胞只表达较长的神经元蛋白亚型。神经元蛋白的缺失导致线粒体生物发生增加，MitoTracker Green染色强度更高。与此同时，原发性皮下白色脂肪细胞中UCP1和线粒体氧化磷酸化关键基因PGC-1α、Cox8b和Cox4的表达增加，表明“褐变”效应。此外，AMPK和ACC的磷酸化增加，表明脂肪酸利用率增加。类似的，但不太明显的，神经元蛋白沉默的作用也在原发性棕色脂肪细胞中被注意到。相反，神经元蛋白的缺失导致基础和胰岛素刺激的葡萄糖摄取和糖原合成的减少，可能是由神经元蛋白沉默后Glut1蛋白的减少介导的。相反，神经元蛋白的缺失对胰岛素信号传导没有影响。综上所述，神经元蛋白似乎是白色脂肪细胞褐变和代谢底物处置的一种新的调节剂。
Failure of white adipose tissue to appropriately store excess metabolic substrate seems to underpin obesity-associated type 2 diabetes. Encouraging “browning” of white adipose has been suggested as a therapeutic strategy to help dispose of excess stored lipid and ameliorate the resulting insulin resistance. Genetic variation at the DNA locus encoding the novel proteolipid neuronatin has been associated with obesity, and we recently observed that neuronatin expression is reduced in subcutaneous adipose tissue from obese humans. Thus, to explore the function of neuronatin further, we used RNAi to silence its expression in murine primary adipocyte cultures and examined the effects on adipocyte phenotype. We found that primary adipocytes express only the longer isoform of neuronatin. Loss of neuronatin led to increased mitochondrial biogenesis, indicated by greater intensity of MitoTracker Green staining. This was accompanied by increased expression of UCP1 and the key genes in mitochondrial oxidative phosphorylation, PGC-1α, Cox8b, and Cox4 in primary subcutaneous white adipocytes, indicative of a “browning” effect. In addition, phosphorylation of AMPK and ACC was increased, suggestive of increased fatty acid utilization. Similar, but less pronounced, effects of neuronatin silencing were also noted in primary brown adipocytes. In contrast, loss of neuronatin caused a reduction in both basal and insulin-stimulated glucose uptake and glycogen synthesis, likely mediated by a reduction in Glut1 protein upon silencing of neuronatin. In contrast, loss of neuronatin had no effect on insulin signaling. In conclusion, neuronatin appears to be a novel regulator of browning and metabolic substrate disposal in white adipocytes.
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对脂肪组织中含有饮食反应基因 Nnat 的基因共表达模块进行生物信息学分析。
影响因子：
--
作者：
Li X;Thomason PA;Withers DJ;Scott J
通讯作者：
Scott J
DOI：
10.1046/j.1365-201x.2003.01162.x
发表时间：
2003-08-01
期刊：
ACTA PHYSIOLOGICA SCANDINAVICA
影响因子：
--
作者：
Hegarty, BD;Furler, SM;Kraegen, EW
通讯作者：
Kraegen, EW
影响因子：
29
作者：
Seale, Patrick;Kajimura, Shingo;Spiegelman, Bruce M.
通讯作者：
Spiegelman, Bruce M.
影响因子：
6.1
作者：
Sharma, Jaiprakash;Rao, Sudheendra N. R.;Jana, Nihar Ranjan
通讯作者：
Jana, Nihar Ranjan
影响因子：
5.2
作者：
Lin, Hsuan-Hwai;Bell, Esther;Uwanogho, Dafe;Perfect, Leo W.;Noristani, Harun;Bates, Thomas J. D.;Snetkov, Vladimir;Price, Jack;Sun, Yuh-Man
通讯作者：
Sun, Yuh-Man