PDF(Pubmed)
Abstract：
OBJECTIVE: Exposure of adipocytes to \'cool\' temperatures often found in the periphery of the body induces expression of Stearoyl-CoA Desaturase-1 (Scd1), an enzyme that converts saturated fatty acids to monounsaturated fatty acids. The goal of this study is to further investigate the roles of Scd in adipocytes.
METHODS: In this study, we employed Scd1 knockout cells and mouse models, along with pharmacological Scd1 inhibition to dissect the enzyme\'s function in adipocyte physiology.
RESULTS: Our study reveals that production of monounsaturated lipids by Scd1 is necessary for fusion of autophagosomes to lysosomes and that with a Scd1-deficiency, autophagosomes accumulate. In addition, Scd1-deficiency impairs lysosomal and autolysosomal acidification resulting in vacuole accumulation and eventual cell death. Blocking autophagosome formation or supplementation with monounsaturated fatty acids maintains vitality of Scd1-deficient adipocytes.
CONCLUSIONS: This study demonstrates the indispensable role of Scd1 in adipocyte survival, with its inhibition in vivo triggering autophagy-dependent cell death and its depletion in vivo leading to the loss of bone marrow adipocytes.
METHODS: In this study, we employed Scd1 knockout cells and mouse models, along with pharmacological Scd1 inhibition to dissect the enzyme\'s function in adipocyte physiology.
RESULTS: Our study reveals that production of monounsaturated lipids by Scd1 is necessary for fusion of autophagosomes to lysosomes and that with a Scd1-deficiency, autophagosomes accumulate. In addition, Scd1-deficiency impairs lysosomal and autolysosomal acidification resulting in vacuole accumulation and eventual cell death. Blocking autophagosome formation or supplementation with monounsaturated fatty acids maintains vitality of Scd1-deficient adipocytes.
CONCLUSIONS: This study demonstrates the indispensable role of Scd1 in adipocyte survival, with its inhibition in vivo triggering autophagy-dependent cell death and its depletion in vivo leading to the loss of bone marrow adipocytes.
摘要：
脂肪细胞暴露于身体周围经常发现的凉爽温度诱导硬脂酰辅酶A去饱和酶-1（Scd1）的表达，将饱和脂肪酸转化为单不饱和脂肪酸的酶。在这项研究中,我们采用了Scd1敲除细胞和小鼠模型，随着药理Scd1抑制，进一步研究Scd1在脂肪细胞中的作用。我们的研究表明，Scd1产生单不饱和脂质是自噬体与溶酶体融合所必需的，而Scd1缺乏时，自噬体积累。此外,Scd1缺乏会损害溶酶体和自溶酶体酸化，导致液泡积累和最终的细胞死亡。阻断自噬体形成或补充单不饱和脂肪酸可保持Scd1缺陷脂肪细胞的活力。一起来看,我们的结果表明，在脂肪细胞中体外抑制Scd1会导致自噬依赖性细胞死亡，和体内消耗导致骨髓脂肪细胞的损失。
