Stearoyl-coenzyme A desaturase 1, sterol regulatory element binding protein-1c and peroxisome proliferator-activated receptor-α:: independent and interactive roles in the regulation of lipid metabolism
Stearoyl-coenzyme A desaturase 1, sterol regulatory element binding protein-1c and peroxisome proliferator-activated receptor-α:: independent and interactive roles in the regulation of lipid metabolism
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DOI：
10.1097/01.mco.0000214564.59815.af
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发表时间：
2006-03-01
影响因子：
3.1
通讯作者：
Ntambi, JM
中科院分区：
文献类型：
--
作者：
Sampath, H;Ntambi, JM
综述目的随着肥胖症发病率的日益增加，糖尿病、胰岛素抵抗和肝脂肪变性等相关并发症也成为主要问题。由于这些条件有一个共同的因素，脂质代谢异常，了解导致异常脂质分配的分子变化已成为关键打击obesity epidemies.Recent发现酶硬脂酰辅酶A去饱和酶1（SCD 1）已被证明是密切参与脂肪生成以及脂质氧化途径。我们用SCD 1（-/-）小鼠模型的研究已经确定，这些动物是瘦的，并且免受瘦素缺乏诱导的肥胖和饮食诱导的肥胖。因此，它们也表现出比野生型小鼠更高的全身胰岛素敏感性。SCD 1（-/-）小鼠具有脂肪生成基因的表达降低和脂质氧化基因的表达增加。控制脂质合成和氧化的主要转录因子分别是固醇调节元件结合蛋白-1c和过氧化物酶体增殖物激活受体-α（PPAR α）。在这里，我们回顾一些研究表明，SCD 1缺乏对全身肥胖的影响可能部分依赖于固醇调节元件结合蛋白-1C，但最有可能独立的过氧化物酶体增殖物激活受体-α。摘要我们的研究结果表明，SCD 1是一个关键的控制器之间的脂肪生成和氧化的脂质分配。虽然关于SCD 1缺失下游的分子变化的一些问题尚未得到回答，但下文概述的研究明确指出SCD 1是对抗肥胖症以及相关并发症的非常有希望的靶点。
Purpose of review With the increasing incidence of obesity today, related complications such as diabetes, insulin resistance and hepatic steatosis are also becoming major concerns. Since these conditions share a common factor, aberrations in lipid metabolism, understanding the molecular changes that lead to abnormal lipid partitioning has become key to combating the obesity epidemic.Recent findings The enzyme stearoyl-coenzyme A desaturase 1 (SCD1) has been shown to be intimately involved in both the lipogenic as well as the lipid oxidative pathways. Our studies with the SCD1(-/-) mouse model have established that these animals are lean and protected from leptin deficiency-induced and diet-induced obesity. Consequently, they also show greater whole body insulin sensitivity than wild-type mice. SCD1(-/-) mice have decreased expression of genes of lipogenesis and increased expression of lipid oxidative genes. The main transcription factors controlling genes of lipid synthesis and oxidation are sterol regulatory element binding protein-1c and peroxisome proliferator-activated receptor-alpha (PPAR alpha), respectively. Here, we review some studies that show that the effects of SCD1 deficiency on whole body adiposity may be partly dependent on sterol regulatory element binding protein-1c, but are most likely independent of peroxisome proliferator-activated receptor-alpha.Summary Our findings indicate that SCD1 is a key controller of lipid partitioning between lipogenesis and oxidation. While some questions regarding the molecular changes downstream of SCD1 deletion are yet to be answered, the studies outlined below clearly point to SCD1 as a highly promising target in combating obesity as well as related complications.