The short-chain fatty acid acetate modulates orexin/hypocretin neurons: A novel mechanism in gut-brain axis regulation of energy homeostasis and feeding.

Autor: Forte N; Institute of Biomolecular Chemistry, National Research Council of Italy, Pozzuoli, Naples, Italy., Marfella B; Institute of Biomolecular Chemistry, National Research Council of Italy, Pozzuoli, Naples, Italy; Department of Biology, University of Naples Federico II, Naples, Italy., Nicois A; Institute of Biomolecular Chemistry, National Research Council of Italy, Pozzuoli, Naples, Italy; Department of Biomolecular Sciences, University of Urbino Carlo Bo, Urbino, Italy., Palomba L; Institute of Biomolecular Chemistry, National Research Council of Italy, Pozzuoli, Naples, Italy; Department of Biomolecular Sciences, University of Urbino Carlo Bo, Urbino, Italy., Paris D; Institute of Biomolecular Chemistry, National Research Council of Italy, Pozzuoli, Naples, Italy., Motta A; Institute of Biomolecular Chemistry, National Research Council of Italy, Pozzuoli, Naples, Italy., Pina Mollica M; Department of Biology, University of Naples Federico II, Naples, Italy; Centro Servizi Metrologici e Tecnologici Avanzati (CeSMA), Complesso Universitario di Monte Sant'Angelo, 80126 Naples, Italy; Task Force on Microbiome Studies, University of Naples Federico II, 80138 Naples, Italy., Di Marzo V; Canada Excellence Research Chair on the Microbiome-Endocannabinoidome Axis in Metabolic Health, Faculty of Medicine and Faculty of Agricultural and Food Sciences, Université Laval, Québec City, QC, Canada. Electronic address: vincenzo.dimarzo@criucpq.ulaval.ca., Cristino L; Institute of Biomolecular Chemistry, National Research Council of Italy, Pozzuoli, Naples, Italy. Electronic address: luigia.cristino@icb.cnr.it.
Jazyk: angličtina
Zdroj: Biochemical pharmacology [Biochem Pharmacol] 2024 Aug; Vol. 226, pp. 116383. Date of Electronic Publication: 2024 Jun 20.
DOI: 10.1016/j.bcp.2024.116383
Abstrakt: The short-chain fatty acids (SCFAs) acetate, propionate and butyrate, the major products of intestinal microbial fermentation of dietary fibres, are involved in fine-tuning brain functions via the gut-brain axis. However, the effects of SCFAs in the hypothalamic neuronal network regulating several autonomic-brain functions are still unknown. Using NMR spectroscopy, we detected a reduction in brain acetate concentrations in the hypothalamus of obese leptin knockout ob/ob mice compared to lean wild-type littermates. Therefore, we investigated the effect of acetate on orexin/hypocretin neurons (hereafter referred as OX or OX-A neurons), a subset of hypothalamic neurons regulating energy homeostasis, which we have characterized in previous studies to be over-activated by the lack of leptin and enhancement of endocannabinoid tone in the hypothalamus of ob/ob mice. We found that acetate reduces food-intake in concomitance with a reduction of orexin neuronal activity in ob/ob mice. This was demonstrated by evaluating food-intake behaviour and orexin-A/c-FOS immunoreactivity coupled with patch-clamp recordings in Hcrt-eGFP neurons, quantification of prepro-orexin mRNA, and immunolabeling of GPR-43, the main acetate receptor. Our data provide new insights into the mechanisms of the effects of chronic dietary supplementation with acetate, or complex carbohydrates, on energy intake and body weight, which may be partly mediated by inhibition of orexinergic neuron activity.
Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
(Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)
Databáze: MEDLINE
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