Perlecan, a heparan sulfate proteoglycan, regulates systemic metabolism with dynamic changes in adipose tissue and skeletal muscle.
Perlecan, a heparan sulfate proteoglycan, regulates systemic metabolism with dynamic changes in adipose tissue and skeletal muscle.
复制标题
DOI：
10.1038/s41598-018-25635-x
复制
发表时间：
2018-05-17
影响因子：
4.6
通讯作者：
Arikawa-Hirasawa E
中科院分区：
文献类型：
--
作者：
Yamashita Y;Nakada S;Yoshihara T;Nara T;Furuya N;Miida T;Hattori N;Arikawa-Hirasawa E
Perlecan （HSPG2）是一种硫酸肝素蛋白多糖，是基底膜的组成成分，参与多种生物活性。在这里，我们展示了perlecan在肥胖和代谢综合征发病中的生理作用。围产期死亡挽救的perlecan基因敲除（Hspg2−/−-Tg）小鼠的白色脂肪组织质量和细胞大小均小于对照组（WT-Tg）小鼠。在Hspg2−/−-Tg小鼠中未检测到异常的脂质沉积，如脂肪肝，并且这些小鼠也消耗更多的脂肪作为能量来源，可能是由于它们激活的脂肪酸氧化。此外，Hspg2−/−-Tg小鼠表现出胰岛素敏感性增加。分子分析显示，Hspg2−/−-Tg小鼠骨骼肌中肌纤维IIA (X)型异构体的数量显著相对增加，线粒体数量较多。此外，perlecan缺陷骨骼肌也有过氧化物酶体增殖物激活受体γ辅助激活因子1- α (PGC1α)蛋白水平升高。运动激活PGC1α表达，诱导线粒体生物合成。因此，perlecan可能通过将肌纤维成分转化为氧化纤维而作为脂质和葡萄糖分解代谢的机械调节剂。我们的数据表明下调perlecan是一种很有希望的控制代谢综合征的策略。
Perlecan (HSPG2), a heparan sulfate proteoglycan, is a component of basement membranes and participates in a variety of biological activities. Here, we show physiological roles of perlecan in both obesity and the onset of metabolic syndrome. The perinatal lethality-rescued perlecan knockout (Hspg2−/−-Tg) mice showed a smaller mass and cell size of white adipose tissues than control (WT-Tg) mice. Abnormal lipid deposition, such as fatty liver, was not detected in the Hspg2−/−-Tg mice, and those mice also consumed more fat as an energy source, likely due to their activated fatty acid oxidation. In addition, the Hspg2−/−-Tg mice demonstrated increased insulin sensitivity. Molecular analysis revealed the significantly relatively increased amount of the muscle fiber type IIA (X) isoform and a larger quantity of mitochondria in the skeletal muscle of Hspg2−/−-Tg mice. Furthermore, the perlecan-deficient skeletal muscle also had elevated levels of peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC1α) protein. PGC1α expression is activated by exercise, and induces mitochondrial biosynthesis. Thus, perlecan may act as a mechano-regulator of catabolism of both lipids and glucose by shifting the muscle fiber composition to oxidative fibers. Our data suggest that downregulation of perlecan is a promising strategy to control metabolic syndrome.
登录
查看更多内容
影响因子：
4.8
作者：
CHAKRAVARTI, S;HORCHAR, T;HASSELL, JR
通讯作者：
HASSELL, JR
影响因子：
4.1
作者：
Hittel DS;Axelson M;Sarna N;Shearer J;Huffman KM;Kraus WE
通讯作者：
Kraus WE
影响因子：
5.2
作者：
Choe SS;Huh JY;Hwang IJ;Kim JI;Kim JB
通讯作者：
Kim JB
影响因子：
3.7
作者：
Bloemberg D;Quadrilatero J
通讯作者：
Quadrilatero J
影响因子：
3.3
作者：
Adams, GR;McCue, SA
通讯作者：
McCue, SA