Integrins and extracellular matrix proteins modulate adipocyte thermogenic capacity.
Integrins and extracellular matrix proteins modulate adipocyte thermogenic capacity.
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DOI：
10.1038/s41598-021-84828-z
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发表时间：
2021-03-08
影响因子：
4.6
通讯作者：
Brey EM
中科院分区：
文献类型：
--
作者：
Gonzalez Porras MA;Stojkova K;Vaicik MK;Pelowe A;Goddi A;Carmona A;Long B;Qutub AA;Gonzalez A;Cohen RN;Brey EM
肥胖和代谢疾病的流行导致发病率和死亡率上升。通过激活棕色或米色脂肪来提高脂肪产热能力是治疗代谢疾病的一种潜在方法。然而，对于局部因素如何控制脂肪细胞命运的了解有限。层粘连蛋白α4（LAMA4）基因缺失突变的小鼠（KO）表现出对肥胖的抵抗以及白色脂肪组织（WAT）中产热脂肪标志物表达增强。在这项研究中，使用液相色谱/串联质谱法评估了在缺乏LAMA4时白色脂肪组织细胞外基质成分的变化。KO小鼠显示出胶原蛋白1A1和3A1以及整合素α7（ITA7）和β1（ITB1）水平较低。在野生型小鼠中，棕色脂肪组织中ITA7 - ITB1和胶原蛋白1A1 - 3A1蛋白水平比白色脂肪组织中低。免疫组织化学染色证实KO - WAT中ITA7水平较低且空间分布不同。在培养研究中，脂肪干细胞分化为米色脂肪12天后，ITA7和LAMA4水平下降，并且在分化过程中敲低ITA7会增加米色化。这些结果表明细胞外基质相互作用调节脂肪细胞的产热能力，并且ITA7在米色脂肪形成中起作用。更好地理解这些相互作用背后的机制可用于改善全身能量代谢和葡萄糖稳态。
Obesity and the metabolic disease epidemic has led to an increase in morbidity and mortality. A rise in adipose thermogenic capacity via activation of brown or beige fat is a potential treatment for metabolic diseases. However, an understanding of how local factors control adipocyte fate is limited. Mice with a null mutation in the laminin α4 (LAMA4) gene (KO) exhibit resistance to obesity and enhanced expression of thermogenic fat markers in white adipose tissue (WAT). In this study, changes in WAT extracellular matrix composition in the absence of LAMA4 were evaluated using liquid chromatography/tandem mass spectrometry. KO-mice showed lower levels of collagen 1A1 and 3A1, and integrins α7 (ITA7) and β1 (ITB1). ITA7-ITB1 and collagen 1A1-3A1 protein levels were lower in brown adipose tissue compared to WAT in wild-type mice. Immunohistochemical staining confirmed lower levels and different spatial distribution of ITA7 in KO-WAT. In culture studies, ITA7 and LAMA4 levels decreased following a 12-day differentiation of adipose-derived stem cells into beige fat, and knock-down of ITA7 during differentiation increased beiging. These results demonstrate that extracellular matrix interactions regulate adipocyte thermogenic capacity and that ITA7 plays a role in beige adipose formation. A better understanding of the mechanisms underlying these interactions can be used to improve systemic energy metabolism and glucose homeostasis.
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影响因子：
5.8
作者：
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通讯作者：
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21.3
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Rossi FM