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Global deletion of lipocalin 2 does not reverse high-fat diet-induced obesity resistance in stearoyl-CoA desaturase-1 skin-specific knockout mice

机译:整体删除lipocalin 2不会逆转高脂饮食诱导的硬脂酰辅酶A去饱和酶1皮肤特异性基因敲除小鼠的肥胖抗性

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摘要

Over the past century, obesity has developed into a paramount health issue that affects millions of people worldwide. Obese individuals have an increased risk to develop other metabolic disorders, such as insulin resistance and atherosclerosis, among others. Previously we determined that mice lacking stearoyl-CoA desaturase-1 (SCD1) enzyme specifically in the skin (SKO) were lean and protected from high-fat diet induced adiposity. Additionally, lipocalin 2 (Lcn2) mRNA was found to be 27-fold higher in the skin of SKO mice compared to control mice. Given reports suggesting that Lcn2 plays a role in protection against diet-induced weight gain, adiposity and insulin resistance, we hypothesized that deletion of Lcn2 alongside the skin-specific SCD1 deficiency would diminish the obesity resistance observed in SKO mice. To test this, we developed mice lacking SCD1 expression in the skin and also lacking Lcn2 expression globally and surprisingly, these mice did not gain significantly more weight than the SKO mice under high-fat diet conditions. Therefore, we conclude that Lcn2 does not mediate the protection against high-fat diet-induced adiposity observed in SKO mice.
机译:在过去的一个世纪中,肥胖已发展成为影响全球数百万人的首要健康问题。肥胖个体发生其他代谢异常(例如胰岛素抵抗和动脉粥样硬化)的风险增加。先前,我们确定缺少在皮肤(SKO)中特异性缺乏硬脂酰-CoA去饱和酶1(SCD1)酶的小鼠是瘦型的,并免受高脂饮食诱导的肥胖症的影响。此外,与对照小鼠相比,SKO小鼠皮肤中的脂蛋白2(Lcn2)mRNA被发现高27倍。给定的报告表明Lcn2在抵抗饮食引起的体重增加,肥胖和胰岛素抵抗中起一定作用,我们假设删除Lcn2以及皮肤特异性SCD1缺乏症会减少SKO小鼠的肥胖抵抗力。为了测试这一点,我们开发了在皮肤中既缺乏SCD1表达又缺乏Lcn2表达的小鼠,而且令人惊讶的是,在高脂饮食条件下,这些小鼠的体重没有显着高于SKO小鼠。因此,我们得出结论,Lcn2不会介导在SKO小鼠中观察到的针对高脂饮食诱导的肥胖的保护作用。

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