PERK-dependent regulation of lipogenesis during mouse mammary gland development and adipocyte differentiation
PERK-dependent regulation of lipogenesis during mouse mammary gland development and adipocyte differentiation
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DOI：
10.1073/pnas.0808517105
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发表时间：
2008-10-21
影响因子：
11.1
通讯作者：
Diehl, J. Alan
中科院分区：
文献类型：
--
作者：
Bobrovnikova-Marjon, Ekaterina;Hatzivassiliou, Georgia;Diehl, J. Alan
内质网应激调节激酶（PERK）在乳腺功能中的作用通过在乳腺上皮中产生靶向缺失来评估。表征表明，PERK是分泌乳汁的乳腺上皮细胞功能成熟所必需的。PERK依赖性信号传导有助于乳腺上皮的脂肪生成分化，并且PERK缺失抑制脂肪生成酶FAS、ACL和SCD 1的持续表达。因此，乳腺组织的脂质含量降低，产生的乳汁的脂质成分改变，导致幼犬生长减弱。与脂肪生成途径的PERK依赖性调节一致，当在有利于脂肪细胞分化的条件下培养时，PERK的丧失抑制了永生化鼠胚胎成纤维细胞中FAS、ACL和SCD 1的表达。这些发现暗示PERK作为脂肪生成途径的生理相关调节剂。
The role of the endoplasmic reticulum stress-regulated kinase, PERK, in mammary gland function was assessed through generation of a targeted deletion in mammary epithelium. Characterization revealed that PERK is required for functional maturation of milk-secreting mammary epithelial cells. PERK-dependent signaling contributes to lipogenic differentiation in mammary epithelium, and perk deletion inhibits the sustained expression of lipogenic enzymes FAS, ACL, and SCD1. As a result, mammary tissue has reduced lipid content and the milk produced has altered lipid composition, resulting in attenuated pup growth. Consistent with PERK-dependent regulation of the lipogenic pathway, loss of PERK inhibits expression of FAS, ACL, and SCD1 in immortalized murine embryonic fibroblasts when cultured under conditions favoring adipocyte differentiation. These findings implicate PERK as a physiologically relevant regulator of the lipogenic pathway.