Abstract：
Weight loss is often followed by weight regain. Characterizing endocrine alterations accompanying weight reduction and regain may disentangle the complex biology of weight-loss maintenance. Here, we profile energy-balance-regulating metabokines and sphingolipids in adults with obesity undergoing an initial low-calorie diet-induced weight loss and a subsequent weight-loss maintenance phase with exercise, glucagon-like peptide-1 (GLP-1) analog therapy, both combined, or placebo. We show that circulating growth differentiation factor 15 (GDF15) and C16:0-C18:0 ceramides transiently increase upon initial diet-induced weight loss. Conversely, circulating fibroblast growth factor 21 (FGF21) is downregulated following weight-loss maintenance with combined exercise and GLP-1 analog therapy, coinciding with increased adiponectin, decreased leptin, and overall decrements in ceramide and sphingosine-1-phosphate levels. Subgroup analyses reveal differential alterations in FGF21-adiponectin-leptin-sphingolipids between weight maintainers and regainers. Clinically, cardiometabolic health outcomes associate with selective metabokine-sphingolipid remodeling signatures. Collectively, our findings indicate distinct FGF21, GDF15, and ceramide responses to diverse phases of weight change and suggest that weight-loss maintenance involves alterations within the metabokine-sphingolipid axis.
摘要：
体重减轻后往往是体重恢复。表征伴随体重减轻和恢复的内分泌改变可能会解开减肥维持的复杂生物学。这里,我们介绍了肥胖成年人的能量平衡调节代谢细胞因子和鞘脂，这些成年人经历了最初的低热量饮食诱导的体重减轻和随后的运动减肥维持阶段，胰高血糖素样肽-1(GLP-1)类似物治疗,两者结合起来，或安慰剂。我们表明，循环生长分化因子15（GDF15）和C16：0-C18：0神经酰胺在初始饮食诱导的体重减轻后会短暂增加。相反，循环成纤维细胞生长因子21（FGF21）在联合运动和GLP-1类似物治疗的减肥维持后下调，与脂联素增加相吻合，减少瘦素,以及神经酰胺和1-磷酸鞘氨醇水平的总体下降。亚组分析揭示了体重维持者和恢复者之间FGF21-脂联素-瘦素-鞘脂的差异变化。临床上,心脏代谢健康结局与选择性代谢因子-鞘脂重塑特征相关.总的来说，我们的研究结果表明,FGF21,GDF15和神经酰胺对体重变化的不同阶段有不同的反应,并提示体重减轻的维持包括代谢因子-鞘脂轴的改变.
