Western diet-induced cognitive and metabolic dysfunctions in aged mice are prevented by rosmarinic acid in a sex-dependent fashion.

Autor: Giona L; Center for Behavioural Sciences and Mental Health, Istituto Superiore di Sanità, Viale Regina Elena 299, 00161 Rome, Italy; Program in Science of Nutrition, Metabolism, Ageing and Gender-Related Diseases, Faculty of Medicine and Surgery, Catholic University of the Sacred Heart, Largo Francesco Vito 1, 00168 Rome, Italy. Electronic address: letizia.giona@guest.iss.it., Musillo C; Center for Behavioural Sciences and Mental Health, Istituto Superiore di Sanità, Viale Regina Elena 299, 00161 Rome, Italy. Electronic address: chiara.musillo@iss.it., De Cristofaro G; Center for Behavioural Sciences and Mental Health, Istituto Superiore di Sanità, Viale Regina Elena 299, 00161 Rome, Italy. Electronic address: gaia.decristofaro1990@gmail.com., Ristow M; Institute of Experimental Endocrinology and Diabetology, Charité Universitätsmedizin Berlin, Berlin D-10117, Germany. Electronic address: michael.ristow@charite.de., Zarse K; Institute of Experimental Endocrinology and Diabetology, Charité Universitätsmedizin Berlin, Berlin D-10117, Germany. Electronic address: ki.zarse@charite.de., Siems K; AnalytiCon Discovery GmbH, 14473 Potsdam, Germany. Electronic address: k.siems@ac-discovery.com., Tait S; Center for Gender-Specific Medicine, Istituto Superiore di Sanità, Viale Regina Elena 299, 00161 Rome, Italy. Electronic address: sabrina.tait@iss.it., Cirulli F; Center for Behavioural Sciences and Mental Health, Istituto Superiore di Sanità, Viale Regina Elena 299, 00161 Rome, Italy. Electronic address: francesca.cirulli@iss.it., Berry A; Center for Behavioural Sciences and Mental Health, Istituto Superiore di Sanità, Viale Regina Elena 299, 00161 Rome, Italy. Electronic address: alessandra.berry@iss.it.
Jazyk: angličtina
Zdroj: Clinical nutrition (Edinburgh, Scotland) [Clin Nutr] 2024 Oct; Vol. 43 (10), pp. 2236-2248. Date of Electronic Publication: 2024 Aug 18.
DOI: 10.1016/j.clnu.2024.08.012
Abstrakt: Background & Aims: Unhealthy lifestyles, such as chronic consumption of a Western Diet (WD), have been associated with increased systemic inflammation and oxidative stress (OS), a condition that may favour cognitive dysfunctions during aging. Polyphenols, such as rosmarinic acid (RA) may buffer low-grade inflammation and OS, characterizing the aging brain that is sustained by WD, promoting healthspan. The aim of this study was to evaluate the ability of RA to prevent cognitive decline in a mouse model of WD-driven unhealthy aging and to gain knowledge on the specific molecular pathways modulated within the brain.
Methods: Aged male and female C57Bl/6N mice were supplemented either with RA or vehicle for 6 weeks. Following 2 weeks on RA they started being administered either with WD or control diet (CD). Successively all mice were tested for cognitive abilities in the Morris water maze (MWM) and emotionality in the elevated plus maze (EPM). Glucose and lipid homeostasis were assessed in trunk blood while the hippocampus was dissected out for RNAseq transcriptomic analysis.
Results: RA prevented insulin resistance in males while protecting both males and females from WD-dependent memory impairment. In the hippocampus, RA modulated OS pathways in males and immune- and sex hormones-related signalling cascades (Lhb and Lhcgr genes) in females. Moreover, RA overall resulted in an upregulation of Glp1r, recently identified as a promising target to prevent metabolic derangements. In addition, we also found an RA-dependent enrichment in nuclear transcription factors, such as NF-κB, GR and STAT3, that have been recently suggested to promote healthspan and longevity by modulating inflammatory and cell survival pathways.
Conclusions: Oral RA supplementation may promote brain and metabolic plasticity during aging through antioxidant and immune-modulating properties possibly affecting the post-reproductive hormonal milieu in a sex-dependent fashion. Thus, its supplementation should be considered in the context of precision medicine as a possible strategy to preserve cognitive functions and to counteract metabolic derangements.
Competing Interests: Conflict of interest K.S. was employed by AnalytiCon Discovery GmbH, Potsdam, Germany. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. All authors have approved the manuscript in its final form.
(Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)
Databáze: MEDLINE
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