Catecholamines stimulate the mobilization of stored triglycerides in adipocytes to provide fatty acids (FAs) for other tissues. However, a large proportion is taken back up and either oxidized or re-esterified. What controls the disposition of these FAs in adipocytes remains unknown. Here, we report that catecholamines redirect FAs for oxidation through the phosphorylation of signal transducer and activator of transcription 3 (STAT3). Adipocyte STAT3 is phosphorylated upon activation of β-adrenergic receptors, and in turn suppresses FA re-esterification to promote FA oxidation. Adipocyte-specific Stat3 KO mice exhibit normal rates of lipolysis, but exhibit defective lipolysis-driven oxidative metabolism, resulting in reduced energy expenditure and increased adiposity when they are on a high-fat diet. This previously unappreciated, non-genomic role of STAT3 explains how sympathetic activation can increase both lipolysis and FA oxidation in adipocytes, revealing a new regulatory axis in metabolism.

儿茶酚胺刺激脂肪细胞中储存的甘油三酯的动员，为其他组织提供脂肪酸（FA）。然而，很大一部分被回收并被氧化或重新酯化。是什么控制着这些 FA 在脂肪细胞中的分布仍然未知。在这里，我们报道儿茶酚胺通过信号转导子和转录激活子 3 (STAT3) 的磷酸化来改变 FA 的氧化方向。脂肪细胞 STAT3 在 β-肾上腺素能受体激活后被磷酸化，进而抑制 FA 再酯化以促进 FA 氧化。脂肪细胞特异性Stat3 KO 小鼠表现出正常的脂肪分解率，但表现出脂肪分解驱动的氧化代谢缺陷，导致高脂肪饮食时能量消耗减少和肥胖增加。 STAT3 的这种先前未被重视的非基因组作用解释了交感神经激活如何增加脂肪细胞中的脂肪分解和 FA 氧化，揭示了代谢中的新调节轴。