Wueest Stephan, Seelig Eleonora, Timper Katharina, Lyngbaek Mark P, Karstoft Kristian, Donath Marc Y, Ellingsgaard Helga, Konrad Daniel
Division of Pediatric Endocrinology and Diabetology, University Children's Hospital, University of Zurich, CH-8032 Zurich, Switzerland.
Children's Research Center, University Children's Hospital, University of Zurich, CH-8032 Zurich, Switzerland.
Metabolites. 2021 Jan 29;11(2):79. doi: 10.3390/metabo11020079.
Human obesity is associated with decreased circulating adiponectin and elevated leptin levels. In vitro experiments and studies in high fat diet (HFD)-fed mice suggest that interleukin-6 (IL-6) may regulate adiponectin and leptin release from white adipose tissue (WAT). Herein, we aimed to investigate whether IL-6 receptor blockade affects the levels of circulating adiponectin and leptin in obese human individuals. To this end, serum samples collected during a multicenter, double-blind clinical trial were analyzed. In the latter study, obese human subjects with or without type 2 diabetes were randomly assigned to recurrent placebo or intravenous tocilizumab (an IL-6 receptor antibody) administration during a 12-week exercise training intervention. Twelve weeks of tocilizumab administration (in combination with exercise training) trend wise enhanced the decrease in circulating leptin levels (-2.7 ± 8.2% in the placebo vs. -20.6 ± 5.6% in tocilizumab, = 0.08) and significantly enhanced the increase in circulating adiponectin (3.4 ± 3.7% in the placebo vs. 27.0 ± 6.6% in tocilizumab, = 0.01). In addition, circulating adiponectin levels were negatively correlated with the homeostatic model assessment of insulin resistance (HOMA-IR), indicating that increased adiponectin levels positively affect insulin sensitivity in people with obesity. In conclusion, IL-6 receptor blockade increases circulating adiponectin levels in people with obesity.
人类肥胖与循环脂联素水平降低和瘦素水平升高有关。体外实验以及对高脂饮食（HFD）喂养小鼠的研究表明，白细胞介素-6（IL-6）可能调节白色脂肪组织（WAT）中脂联素和瘦素的释放。在此，我们旨在研究IL-6受体阻断是否会影响肥胖个体的循环脂联素和瘦素水平。为此，我们分析了在一项多中心、双盲临床试验中收集的血清样本。在后者的研究中，患有或不患有2型糖尿病的肥胖人类受试者在为期12周的运动训练干预期间被随机分配接受反复的安慰剂或静脉注射托珠单抗（一种IL-6受体抗体）。给药12周的托珠单抗（联合运动训练）在趋势上增强了循环瘦素水平的降低（安慰剂组为-2.7±8.2%，托珠单抗组为-20.6±5.6%，P = 0.08），并显著增强了循环脂联素的增加（安慰剂组为3.4±3.7%，托珠单抗组为27.0±6.6%，P = 0.01）。此外，循环脂联素水平与胰岛素抵抗稳态模型评估（HOMA-IR）呈负相关，这表明脂联素水平升高对肥胖人群的胰岛素敏感性有积极影响。总之，IL-6受体阻断可提高肥胖人群的循环脂联素水平。
