Department of Internal Medicine, School of Dentistry, Health Sciences University of Hokkaido, 1757, Kanazawa, Ishikari-Toubetsu, Hokkaido 061-0023, Japan.
Biochem Biophys Res Commun. 2013 Feb 1;431(1):25-30. doi: 10.1016/j.bbrc.2012.12.112. Epub 2013 Jan 3.
Lipin-1 plays crucial roles in the regulation of lipid metabolism and cell differentiation in adipocytes. In obesity, adipose lipin-1 mRNA expression is decreased and positively correlated with systemic insulin sensitivity. Amelioration of the lipin-1 depletion might be improved dysmetabolism. Although some cytokines such as TNF-α and interleukin-1β reduces adipose lipin-1 expression, the mechanism of decreased adipose lipin-1 expression in obesity remains unclear. Recently, endoplasmic reticulum (ER) stress is implicated in the pathogenesis of obesity. Here we investigated the role of ER stress on the lipin-1 expression in 3T3-L1 adipocytes. We demonstrated that lipin-1 expression was suppressed by the treatment with ER stress inducers (tunicamycin and thapsigargin) at transcriptional level. We also showed that constitutive lipin-1 expression could be maintained by peroxisome proliferator-activated receptor-γ in 3T3-L1 adipocytes. Activation of peroxisome proliferator-activated receptor-γ recovered the ER stress-induced lipin-1 suppression. These results suggested that ER stress might be involved in the pathogenesis of obesity through lipin-1 depletion.
脂肪组织磷酸二酯酶 1 基因（Lipin-1）在脂肪细胞的脂质代谢和细胞分化的调节中起着关键作用。在肥胖中，脂肪组织 Lipin-1 mRNA 的表达减少，与全身胰岛素敏感性呈正相关。改善 Lipin-1 的耗竭可能会改善代谢紊乱。虽然一些细胞因子，如 TNF-α 和白细胞介素-1β，可降低脂肪组织 Lipin-1 的表达，但肥胖中脂肪组织 Lipin-1 表达减少的机制尚不清楚。最近，内质网（ER）应激与肥胖的发病机制有关。在这里，我们研究了 ER 应激对 3T3-L1 脂肪细胞中 Lipin-1 表达的作用。我们证明，内质网应激诱导剂（衣霉素和 thapsigargin）可在转录水平抑制 Lipin-1 的表达。我们还表明，过氧化物酶体增殖物激活受体-γ（PPAR-γ）可在 3T3-L1 脂肪细胞中维持组成型 Lipin-1 的表达。PPAR-γ 的激活可恢复 ER 应激诱导的 Lipin-1 抑制。这些结果表明，通过 Lipin-1 的耗竭，内质网应激可能参与肥胖的发病机制。
