The development of cardiometabolic complications during obesity is strongly associated with chronic latent inflammation in hypertrophied adipose tissue (AT). IL-4 is an anti-inflammatory cytokine, playing a protective role against insulin resistance, glucose intolerance and weight gain. The positive effects of IL-4 are associated not only with the activation of anti-inflammatory immune cells in AT, but also with the modulation of adipocyte metabolism. IL-4 is known to activate lipolysis and glucose uptake in adipocytes, but the precise regulatory mechanisms and physiological significance of these processes remain unclear. In this study, we detail IL-4 effects on glucose and triacylglycerides (TAGs) metabolism and propose mechanisms of IL-4 metabolic action in adipocytes. We have shown that IL-4 activates glucose oxidation, lipid droplet (LD) fragmentation, lipolysis and thermogenesis in mature 3T3-L1 adipocytes. We found that lipolysis was not accompanied by fatty acids (FAs) release from adipocytes, suggesting FA re-esterification. Moreover, glucose oxidation and thermogenesis stimulation depended on adipocyte triglyceride lipase (ATGL) activity, but not the uncoupling protein (UCP1) expression. Based on these data, IL-4 may activate the futile TAG–FA cycle in adipocytes, which enhances the oxidative activity of cells and heat production. Thus, the positive effect of IL-4 on systemic metabolism can be the result of the activation of non-canonical thermogenic mechanism in AT, increasing TAG turnover and utilization of excessive glucose.

中文翻译：

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IL-4 激活白色脂肪细胞中无用的三酰甘油循环以利用葡萄糖

肥胖期间心脏代谢并发症的发生与肥大脂肪组织（AT）中的慢性潜在炎症密切相关。IL-4是一种抗炎细胞因子，对胰岛素抵抗、葡萄糖耐受不良和体重增加发挥保护作用。IL-4的积极作用不仅与AT中抗炎免疫细胞的激活有关，还与脂肪细胞代谢的调节有关。已知 IL-4 可以激活脂肪细胞中的脂肪分解和葡萄糖摄取，但这些过程的精确调节机制和生理意义仍不清楚。在这项研究中，我们详细介绍了 IL-4 对葡萄糖和三酰甘油 (TAG) 代谢的影响，并提出了 IL-4 在脂肪细胞中代谢作用的机制。我们已经证明，IL-4 可激活成熟 3T3-L1 脂肪细胞中的葡萄糖氧化、脂滴 (LD) 碎裂、脂肪分解和生热作用。我们发现脂肪分解并不伴随脂肪细胞释放脂肪酸（FA），这表明 FA 再酯化。此外，葡萄糖氧化和生热刺激取决于脂肪细胞甘油三酯脂肪酶（ATGL）的活性，而不是解偶联蛋白（UCP1）的表达。基于这些数据，IL-4可能激活脂肪细胞中无效的TAG-FA循环，从而增强细胞的氧化活性和产热。因此，IL-4对全身代谢的积极作用可能是AT中非典型生热机制激活、增加TAG周转和过量葡萄糖利用的结果。