Absence of functional leptin receptor isoforms in the POUND (Lepr(db/lb)) mouse is associated with muscle atrophy and altered myoblast proliferation and differentiation.
Absence of functional leptin receptor isoforms in the POUND (Lepr(db/lb)) mouse is associated with muscle atrophy and altered myoblast proliferation and differentiation.
复制标题
DOI：
10.1371/journal.pone.0072330
复制
发表时间：
2013
期刊：
影响因子：
3.7
通讯作者：
Hamrick MW
中科院分区：
文献类型：
--
作者：
Arounleut P;Bowser M;Upadhyay S;Shi XM;Fulzele S;Johnson MH;Stranahan AM;Hill WD;Isales CM;Hamrick MW
瘦素受体在人体骨骼肌中含量丰富，但瘦素在肌肉生长、发育和衰老中的作用尚不清楚。在这里，我们利用一种新的缺乏所有功能瘦素受体亚型的小鼠模型(庞氏小鼠，Leprdb/Lb)来确定瘦素在骨骼肌中的作用。检测了肥胖小鼠的骨骼肌质量和纤维直径，并通过原代成肌细胞培养来确定瘦素信号改变对成肌细胞增殖和分化的影响。采用酶联免疫吸附试验、基因芯片整合通路分析和反相蛋白分析等方法研究瘦素受体缺陷对细胞信号转导途径的影响。结果表明，与野生型对照相比，肥胖小鼠的骨骼肌质量和纤维直径减少了30%-40%。原代成肌细胞培养显示，与正常小鼠相比，肥胖小鼠的增殖减少，MyoD和Mygenin的表达减少。Leptin治疗促进了成年(12个月)和老年(24个月)野生型小鼠肌肉原代成肌细胞的增殖，并且Leptin增加了老年原代成肌细胞MyoD和Mygenin的表达。ELISA法和蛋白质阵列显示，与IGF-1/Akt和MAPK/MEK信号通路相关的分子在缺乏功能性瘦素受体的小鼠后肢肌肉中的表达发生了变化。这些数据支持这样一种假设，即脂肪因子瘦素是调节骨骼肌质量的关键因素，瘦素可以直接作用于周围组织中的瘦素受体，调节细胞的增殖和分化。
Leptin receptors are abundant in human skeletal muscle, but the role of leptin in muscle growth, development and aging is not well understood. Here we utilized a novel mouse model lacking all functional leptin receptor isoforms (POUND mouse, Leprdb/lb) to determine the role of leptin in skeletal muscle. Skeletal muscle mass and fiber diameters were examined in POUND mice, and primary myoblast cultures were used to determine the effects of altered leptin signaling on myoblast proliferation and differentiation. ELISA assays, integrated pathway analysis of mRNA microarrays, and reverse phase protein analysis were performed to identify signaling pathways impacted by leptin receptor deficiency. Results show that skeletal muscle mass and fiber diameter are reduced 30–40% in POUND mice relative to wild-type controls. Primary myoblast cultures demonstrate decreased proliferation and decreased expression of both MyoD and myogenin in POUND mice compared to normal mice. Leptin treatment increased proliferation in primary myoblasts from muscles of both adult (12 months) and aged (24 months) wild-type mice, and leptin increased expression of MyoD and myogenin in aged primary myoblasts. ELISA assays and protein arrays revealed altered expression of molecules associated with the IGF-1/Akt and MAPK/MEK signaling pathways in muscle from the hindlimbs of mice lacking functional leptin receptors. These data support the hypothesis that the adipokine leptin is a key factor important for the regulation of skeletal muscle mass, and that leptin can act directly on its receptors in peripheral tissues to regulate cell proliferation and differentiation.
登录
查看更多内容
激活素A-乳腺抑制素系统对衰老的骨骼和肌肉祖细胞的影响。
影响因子：
3.9
作者：
Bowser, Matthew;Herberg, Samuel;Arounleut, Phonepasong;Shi, Xingming;Fulzele, Sadanand;Hill, William D.;Isales, Carlos M.;Hamrick, Mark W.
通讯作者：
Hamrick, Mark W.
影响因子：
6.7
作者：
Narici, Marco V.;Maffulli, Nicola
通讯作者：
Maffulli, Nicola
影响因子：
5.8
作者：
Chan, Jean L.;Williams, Catherine J.;Mantzoros, Christos S.
通讯作者：
Mantzoros, Christos S.
影响因子：
4.8
作者：
Amirouche, Adel;Durieux, Anne-Cecile;Freyssenet, Damien
通讯作者：
Freyssenet, Damien
影响因子：
4.1
作者：
Hamrick, MW;Pennington, C;Isales, C
通讯作者：
Isales, C