Gianoli Stefano, Tang Justin, Odegard Kirsten C, Yuki Koichi, Koutsogiannaki Sophia
Department of Anesthesiology, Critical Care and Pain Medicine, Cardiac Anesthesia Division, Boston Childrens Hospital, 300 Longwood Ave, Boston, MA, 02115, USA.
Department of Anaesthesia, Harvard Medical School, Boston, MA, 02115, USA.
Crit Care. 2025 Jul 12;29(1):300. doi: 10.1186/s13054-025-05516-2.
Adiponectin, a key adipokine primarily secreted by adipocytes, plays crucial roles in metabolic homeostasis and inflammation, exhibiting anti-diabetic, anti-atherogenic, and anti-inflammatory properties. Its various isoforms and signaling via receptors like AdipoR1, AdipoR2, and T-cadherin contribute to its diverse biological functions. Sepsis is a life-threatening syndrome triggered by a dysregulated host response to infection, leading to systemic inflammation, multi-organ failure, and high mortality, currently lacking specific treatments. Preclinical studies largely suggest a protective role for adiponectin, demonstrating that its deficiency exacerbates inflammation and endothelial dysfunction, while its administration or agonism improves outcomes in experimental sepsis models. Clinical findings, however, present a complex picture, with inconsistent correlations between adiponectin levels and sepsis outcomes reported, suggesting its potential as a dynamic biomarker influenced by disease stage, patient heterogeneity, and isoforms, rather than a simple prognostic factor. Notably, glucagon-like peptide-1 receptor agonists (GLP-1RAs), used in obesity and diabetes management, have been shown to increase adiponectin levels, linking metabolic therapies to potential sepsis immunomodulation. Consequently, targeting adiponectin signaling, either directly with adiponectin mimics like AdipoRon or indirectly via strategies like GLP-1RA administration, represents a promising therapeutic approach for sepsis. Harnessing the adiponectin axis holds potential for advancing precision medicine in critical care, necessitating further research into adiponectin-based interventions and synergistic metabolic therapies to improve sepsis outcomes.
脂联素是主要由脂肪细胞分泌的一种关键脂肪因子，在代谢稳态和炎症中发挥着至关重要的作用，具有抗糖尿病、抗动脉粥样硬化和抗炎特性。其各种异构体以及通过脂联素受体1（AdipoR1）、脂联素受体2（AdipoR2）和T-钙黏蛋白等受体的信号传导促成了其多样的生物学功能。脓毒症是一种由宿主对感染的反应失调引发的危及生命的综合征，会导致全身炎症、多器官功能衰竭和高死亡率，目前缺乏特效治疗方法。临床前研究大多表明脂联素具有保护作用，证明其缺乏会加剧炎症和内皮功能障碍，而给予脂联素或使用其激动剂则可改善实验性脓毒症模型的预后。然而，临床研究结果呈现出复杂的情况，报道的脂联素水平与脓毒症预后之间的相关性并不一致，这表明它有可能是一种受疾病阶段、患者异质性和异构体影响的动态生物标志物，而非简单的预后因素。值得注意的是，用于肥胖症和糖尿病管理的胰高血糖素样肽-1受体激动剂（GLP-1RAs）已被证明可提高脂联素水平，将代谢疗法与潜在的脓毒症免疫调节联系起来。因此，直接使用如AdipoRon这样的脂联素模拟物或通过给予GLP-1RAs等策略间接靶向脂联素信号传导，代表了一种有前景的脓毒症治疗方法。利用脂联素轴在危重症精准医学方面具有潜力，有必要进一步研究基于脂联素的干预措施和协同代谢疗法以改善脓毒症预后。
