Brown adipose tissue (BAT) plays a key role in energy expenditure through its thermogenic function, making its activation a popular target to reduce obesity. We recently reported that male mice housed at thermoneutrality with uncoupling protein 1 (UCP1) deficiency had increased weight gain and glucose intolerance, but eicosapentaenoic acid (EPA) ameliorated these effects.

Whether female mice respond similarly to lack of UCP1 and to EPA remains unknown. We hypothesize that the effects of EPA on BAT activation are independent of UCP1 expression. We used female wild type (WT) and UCP1 knockout (KO) mice housed at thermoneutrality (30°C) as an obesogenic environment and fed them high fat (HF) diets with or without EPA for up to 14 weeks. Body weight (BW), body composition, and insulin and glucose tolerance tests were performed during the feeding trial. At termination, serum and BAT were harvested for further analyses. Mice in the KO-EPA group had significantly lower BW than KO-HF mice. In addition, KO-HF mice displayed significantly impaired glucose tolerance compared to their WT-HF littermates. However, EPA significantly enhanced glucose clearance in the KO mice compared to KO-HF mice. Protein levels of the mitochondrial cytochrome C oxidase subunits I, II, and IV were significantly lower in KO mice compared to WT. Our findings support that ablation of UCP1 is detrimental to energy metabolism of female mice in thermoneutral conditions. However, unexpectedly, EPA's protective effects against diet-induced obesity and glucose intolerance in these mice were independent of UCP1.

棕色脂肪组织 (BAT) 通过其产热功能在能量消耗中发挥关键作用，使其激活成为减少肥胖的热门目标。我们最近报道，在热中性条件下饲养的解偶联蛋白 1 (UCP1) 缺乏的雄性小鼠体重增加和葡萄糖不耐受增加，但二十碳五烯酸 (EPA) 改善了这些影响。

雌性小鼠对缺乏 UCP1 和对 EPA 的反应是否相似仍然未知。我们假设 EPA 对 BAT 激活的影响与 UCP1 表达无关。我们使用雌性野生型 (WT) 和 UCP1 基因敲除 (KO) 小鼠饲养在热中性 (30°C) 作为致肥胖环境，并用含或不含 EPA 的高脂肪 (HF) 饮食喂养它们长达 14 周。在喂养试验期间进行体重 (BW)、身体成分以及胰岛素和葡萄糖耐量测试。在终止时，收集血清和 BAT 用于进一步分析。KO-EPA 组小鼠的 BW 明显低于 KO-HF 小鼠。此外，与 WT-HF 同窝小鼠相比，KO-HF 小鼠的葡萄糖耐量显着降低。然而，与 KO-HF 小鼠相比，EPA 显着增强了 KO 小鼠的葡萄糖清除率。与 WT 相比，KO 小鼠的线粒体细胞色素 C 氧化酶亚基 I、II 和 IV 的蛋白质水平显着降低。我们的研究结果支持 UCP1 的消融对热中性条件下雌性小鼠的能量代谢有害。然而，出乎意料的是，EPA 在这些小鼠中对饮食诱导的肥胖和葡萄糖不耐受的保护作用与 UCP1 无关。