Centro de Endocrinología Experimental y Aplicada (CENEXA-UNLP-CONICET-CICPBA), University of La Plata Medical School, La Plata 1900, Argentina.
Instituto de Estudios Inmunológicos y Fisiopatológicos (IIFP-UNLP-CONICET-CICPBA), School of Sciences, University of La Plata, La Plata 1900, Argentina.
Int J Mol Sci. 2024 Oct 31;25(21):11741. doi: 10.3390/ijms252111741.
White adipose tissue (WAT) and the gut are involved in the development of neuroinflammation when an organism detects any kind of injury, thereby triggering metainflammation. In fact, the autonomous nervous system innervates both tissues, although the complex role played by the integrated sympathetic, parasympathetic, and enteric nervous system functions have not been fully elucidated. Our aims were to investigate the participation of inflamed WAT and the gut in neuroinflammation. Firstly, we conducted an analysis into how inflamed peripheral WAT plays a key role in the triggering of metainflammation. Indeed, this included the impact of the development of local insulin resistance and its metabolic consequences, a serious hypothalamic dysfunction that promotes neurodegeneration. Then, we analyzed the gut-brain axis dysfunction involved in neuroinflammation by examining cell interactions, soluble factors, the sensing of microbes, and the role of dysbiosis-related mechanisms (intestinal microbiota and mucosal barriers) affecting brain functions. Finally, we targeted the physiological crosstalk between cells of the brain-WAT-gut axis that restores normal tissue homeostasis after injury. We concluded the following: because any injury can result not only in overall insulin resistance and dysbiosis, which in turn can impact upon the brain, but that a high-risk of the development of neuroinflammation-induced neurodegenerative disorder can also be triggered. Thus, it is imperative to avoid early metainflammation by applying appropriate preventive (e.g., lifestyle and diet) or pharmacological treatments to cope with allostasis and thus promote health homeostasis.
白色脂肪组织 (WAT) 和肠道参与机体检测到任何损伤时的神经炎症发生，从而引发代谢炎症。事实上，自主神经系统支配着这两种组织，尽管交感神经、副交感神经和肠神经系统的综合功能所起的复杂作用尚未完全阐明。我们的目的是研究炎症性 WAT 和肠道在神经炎症中的参与作用。首先，我们分析了炎症性外周 WAT 如何在触发代谢炎症中发挥关键作用。实际上，这包括局部胰岛素抵抗发展及其代谢后果的影响，这是一种严重的下丘脑功能障碍，会促进神经退行性变。然后，我们通过检查细胞相互作用、可溶性因子、微生物感知以及与菌群失调相关的机制（肠道微生物群和粘膜屏障）对大脑功能的影响，分析了涉及神经炎症的肠道-脑轴功能障碍。最后，我们针对脑-WAT-肠道轴细胞之间的生理串扰进行了研究，这些串扰在损伤后恢复了正常的组织稳态。我们得出以下结论：因为任何损伤不仅会导致整体胰岛素抵抗和菌群失调，进而影响大脑，而且还会引发神经炎症诱导的神经退行性疾病的高风险。因此，通过应用适当的预防（例如生活方式和饮食）或药物治疗来应对体内平衡，从而促进健康稳态，避免早期代谢炎症至关重要。
