Velloso Licio A, Donato Jose
Laboratory of Cell Signalling‑Obesity and Comorbidities Research Center, University of Campinas, Campinas, Brazil.
National Institute of Science and Technology on Neuroimmunomodulation, Campinas, Brazil.
J Obes Metab Syndr. 2024 Dec 30;33(4):302-313. doi: 10.7570/jomes24032. Epub 2024 Dec 6.
While inflammation is a crucial response in injury repair and tissue regeneration, chronic inflammation is a prevalent feature in various chronic, non-communicable diseases such as obesity, diabetes, and cancer and in cardiovascular and neurodegenerative diseases. Long-term inflammation considerably affects disease prevalence, quality of life, and longevity. Our research indicates that the growth hormone/insulin-like growth factor 1 (GH/IGF-1) axis is a pivotal regulator of inflammation in some tissues, including the hypothalamus, which is a key player in systemic metabolism regulation. Moreover, the GH/IGF-1 axis is strongly linked to longevity, as GH- or GH receptor-deficient mice live approximately twice as long as wild-type animals and exhibit protection against aging-induced inflammation. Conversely, GH excess leads to increased neuroinflammation and reduced longevity. Our review studies the associations between the GH/IGF-1 axis, inflammation, and aging, with a particular focus on evidence suggesting that GH receptor signaling directly induces hypothalamic inflammation. This finding underscores the significant impact of changes in the GH axis on metabolism and on the predisposition to chronic, non-communicable diseases.
虽然炎症是损伤修复和组织再生中的关键反应，但慢性炎症却是肥胖、糖尿病和癌症等各种慢性非传染性疾病以及心血管疾病和神经退行性疾病中的普遍特征。长期炎症会极大地影响疾病的患病率、生活质量和寿命。我们的研究表明，生长激素/胰岛素样生长因子1（GH/IGF-1）轴是包括下丘脑在内的某些组织中炎症的关键调节因子，下丘脑是全身代谢调节的关键参与者。此外，GH/IGF-1轴与长寿密切相关，因为缺乏GH或GH受体的小鼠寿命约为野生型动物的两倍，并且表现出对衰老诱导炎症的保护作用。相反，GH过量会导致神经炎症增加和寿命缩短。我们的综述研究了GH/IGF-1轴、炎症和衰老之间的关联，特别关注表明GH受体信号直接诱导下丘脑炎症的证据。这一发现强调了GH轴变化对代谢以及对慢性非传染性疾病易感性的重大影响。
