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Review

Physiopathological Roles of White Adiposity and Gut Functions in Neuroinflammation

by
Eduardo Spinedi
1,*,† and
Guillermo Horacio Docena
2,*,†
1
Centro de Endocrinología Experimental y Aplicada (CENEXA-UNLP-CONICET-CICPBA), University of La Plata Medical School, La Plata 1900, Argentina
2
Instituto de Estudios Inmunológicos y Fisiopatológicos (IIFP-UNLP-CONICET-CICPBA), School of Sciences, University of La Plata, La Plata 1900, Argentina
*
Authors to whom correspondence should be addressed.
These authors contributed equally to this work.
Int. J. Mol. Sci. 2024, 25(21), 11741; https://doi.org/10.3390/ijms252111741
Submission received: 7 August 2024 / Revised: 23 September 2024 / Accepted: 8 October 2024 / Published: 31 October 2024

Abstract

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.
Keywords: neuroinflammation; hypertrophic white adiposity; insulin resistance; diabetes mellitus; neurodegenerative diseases; central and autonomic nervous systems; immune system; gut–brain axis; microbiota; dysbiosis; brain–WAT–gut axis neuroinflammation; hypertrophic white adiposity; insulin resistance; diabetes mellitus; neurodegenerative diseases; central and autonomic nervous systems; immune system; gut–brain axis; microbiota; dysbiosis; brain–WAT–gut axis

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MDPI and ACS Style

Spinedi, E.; Docena, G.H. Physiopathological Roles of White Adiposity and Gut Functions in Neuroinflammation. Int. J. Mol. Sci. 2024, 25, 11741. https://doi.org/10.3390/ijms252111741

AMA Style

Spinedi E, Docena GH. Physiopathological Roles of White Adiposity and Gut Functions in Neuroinflammation. International Journal of Molecular Sciences. 2024; 25(21):11741. https://doi.org/10.3390/ijms252111741

Chicago/Turabian Style

Spinedi, Eduardo, and Guillermo Horacio Docena. 2024. "Physiopathological Roles of White Adiposity and Gut Functions in Neuroinflammation" International Journal of Molecular Sciences 25, no. 21: 11741. https://doi.org/10.3390/ijms252111741

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