Aerobic Exercise Training Reduces Atherogenesis Induced by Low-Sodium Diet in LDL Receptor Knockout Mice

Bochi, Ana Paula Garcia; Ferreira, Guilherme da Silva; Bianco, Vanessa Del; Pinto, Paula Ramos; Rodrigues, Letícia G.; Trevisani, Mayara da Silva; Furukawa, Luzia Naôko Shinohara; Bispo, Kely Cristina Soares; Silva, Alexandre A. da; Velosa, Ana Paula Pereira; Nakandakare, Edna Regina; Machado, Ubiratan Fabres; Teodoro, Walcy Paganelli Rosolia; Passarelli, Marisa; Catanozi, Sérgio

doi:10.3390/antiox11102023

Cited by 3 publications

(1 citation statement)

References 63 publications

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“…While the LSD effects on the gene and protein expression have been reported in numerous studies (e.g., [99][100][101]), this is the first time, to our knowledge, that remodeling of the gene transcriptomic networks is reported. As shown in Figures 8-10, the LSDinduced remodeling affects the gene expression intercoordination both within functional pathways and between interacting pathways.…”

Section: Discussionmentioning

confidence: 74%

Low-Salt Diet Regulates the Metabolic and Signal Transduction Genomic Fabrics, and Remodels the Cardiac Normal and Chronic Pathological Pathways

Iacobas,

Allen,

Iacobas

2024

CIMB

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Low-salt diet (LSD) is a constant recommendation to hypertensive patients, but the genomic mechanisms through which it improves cardiac pathophysiology are still not fully understood. Our publicly accessible transcriptomic dataset of the left ventricle myocardium of adult male mice subjected to prolonged LSD or normal diet was analyzed from the perspective of the Genomic Fabric Paradigm. We found that LSD shifted the metabolic priorities by increasing the transcription control for fatty acids biosynthesis while decreasing it for steroid hormone biosynthesis. Moreover, LSD remodeled pathways responsible for cardiac muscle contraction (CMC), chronic Chagas (CHA), diabetic (DIA), dilated (DIL), and hypertrophic (HCM) cardiomyopathies, and their interplays with the glycolysis/glucogenesis (GLY), oxidative phosphorylation (OXP), and adrenergic signaling in cardiomyocytes (ASC). For instance, the statistically (p < 0.05) significant coupling between GLY and ASC was reduced by LSD from 13.82% to 2.91% (i.e., −4.75×), and that of ASC with HCM from 10.50% to 2.83% (−3.71×). The substantial up-regulation of the CMC, ASC, and OXP genes, and the significant weakening of the synchronization of the expression of the HCM, CHA, DIA, and DIL genes within their respective fabrics justify the benefits of the LSD recommendation.

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Section: Discussionmentioning

confidence: 74%

Low-Salt Diet Regulates the Metabolic and Signal Transduction Genomic Fabrics, and Remodels the Cardiac Normal and Chronic Pathological Pathways

Iacobas,

Allen,

Iacobas

2024

CIMB

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Mouse PAW: reverse-translating the FINGER multimodal lifestyle intervention enhances synaptic plasticity and cognition in adult wild type female mice

Alanko,

Eroli,

Végvári

et al. 2024

Preprint

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Background: Targeting multiple risk factors through preventive interventions can halt the onset or progression of dementia. The clinical efficacy of this approach was shown in the multimodal FINGER trial, yet knowledge of the underlying biological mechanisms is limited. In the current study, we applied for the first time a multimodal lifestyle intervention in mice to study effects on cognition and associated molecular pathways. Methods: We have established a novel experimental model, the lifestyle intervention PAW (Prevention of Alzheimer's by a Multimodal Lifestyle Protocol - Working-mechanisms for Memory Gains) in mice. In this model, we combined different modalities of intervention aiming to achieve synergistic effects. The animals were given access to running wheels (voluntary exercise), Fortasyn Connect (a medical food that slows disease progression in early Alzheimer's disease), and they were subjected to cognitive training in an IntelliCage environment (PAW group). To separately investigate the effects of pharmacological vascular management as a preventive measure, another group of mice was given Atorvastatin and Enalapril (cholesterol and blood pressure lowering pharmaceuticals, respectively) dosed in the diet (Pharma group). Control mice were housed in normal conditions. We included 12 wild type C57BL/6J female mice 6.5 months of age per group. The full intervention lasted for 8 weeks. Blood pressure was measured at baseline and the end of the intervention. All mice underwent a battery of behavioural testing after the eight weeks of intervention. Hippocampi were dissected for proteomics analysis. Results: During the intervention, the PAW group actively participated in the intervention by learning the different cognitive training programs and by using the running wheels. At the end of the intervention, the PAW group showed a lowering of blood pressure to a similar extent as in the Pharma group (systolic 158 mmHg to 139 mmHg, p = 0.003, and 163 mmHg to 136 mmHg, p = 0.042, respectively). Furthermore, the PAW group displayed a better short-term spatial working memory compared to the control group as assessed by the spontaneous alternation in the Y maze test (66.5% and 56.7%, respectively, p = 0.036). Proteomic analysis of the hippocampi and downstream bioinformatic analysis revealed that several pathways were upregulated in the PAW mice including synaptogenesis (Z = 4.27, p = 1.26E-18) and glutamate binding, activation of AMPA receptors and synaptic plasticity (Z = 3.74, p = 3.16E-19). Conclusions: Our findings suggest that the PAW model effectively mimics the clinical effects of multimodal lifestyle dementia prevention, and further demonstrates the activation of hippocampal-specific molecular drivers of memory gains.

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Aerobic Exercise Training Protects Against Insulin Resistance, Despite Low-Sodium Diet-Induced Increased Inflammation and Visceral Adiposity

Del Bianco,

Ferreira,

Bochi

et al. 2024

IJMS

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Dietary sodium restriction increases plasma triglycerides (TG) and total cholesterol (TC) concentrations as well as causing insulin resistance and stimulation of the renin-angiotensin-aldosterone system (RAAS) and the sympathetic nervous system. Stimulation of the angiotensin II type-1 receptor (AT1) is associated with insulin resistance, inflammation, and the inhibition of adipogenesis. The current study investigated whether aerobic exercise training (AET) mitigates or inhibits the adverse effects of dietary sodium restriction on adiposity, inflammation, and insulin sensitivity in periepididymal adipose tissue. LDL receptor knockout mice were fed either a normal-sodium (NS; 1.27% NaCl) or a low-sodium (LS; 0.15% NaCl) diet and were either subjected to AET for 90 days or kept sedentary. Body mass, blood pressure (BP), hematocrit, plasma TC, TG, glucose and 24-hour urinary sodium (UNa) concentrations, insulin sensitivity, lipoprotein profile, histopathological analyses, and gene and protein expression were determined. The results were evaluated using two-way ANOVA. Differences were not observed in BP, hematocrit, diet consumption, and TC. The LS diet was found to enhance body mass, insulin resistance, plasma glucose, TG, LDL-C, and VLDL-TG and reduce UNa, HDL-C, and HDL-TG, showing a pro-atherogenic lipid profile. In periepididymal adipose tissue, the LS diet increased tissue mass, TG, TC, AT1 receptor, pro-inflammatory macro-phages contents, and the area of adipocytes; contrarily, the LS diet decreased anti-inflammatory macrophages, protein contents and the transcription of genes related to insulin sensitivity. The AET prevented insulin resistance, but did not protect against dyslipidemia, adipose tissue pro-inflammatory profile, increased tissue mass, AT1 receptor expression, TG, and TC induced by the LS diet.

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Aerobic Exercise Training Reduces Atherogenesis Induced by Low-Sodium Diet in LDL Receptor Knockout Mice

Cited by 3 publications

References 63 publications

Low-Salt Diet Regulates the Metabolic and Signal Transduction Genomic Fabrics, and Remodels the Cardiac Normal and Chronic Pathological Pathways

Low-Salt Diet Regulates the Metabolic and Signal Transduction Genomic Fabrics, and Remodels the Cardiac Normal and Chronic Pathological Pathways

Mouse PAW: reverse-translating the FINGER multimodal lifestyle intervention enhances synaptic plasticity and cognition in adult wild type female mice

Aerobic Exercise Training Protects Against Insulin Resistance, Despite Low-Sodium Diet-Induced Increased Inflammation and Visceral Adiposity

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