Olive- and Coconut-Oil-Enriched Diets Decreased Secondary Bile Acids and Regulated Metabolic and Transcriptomic Markers of Brain Injury in the Frontal Cortexes of NAFLD Pigs

Maj, Magdalena; Gehani, Tanvi R.; Immoos, Chad E.; Medrano, Mikaelah S.; Fanter, Rob; Strand, Christine R.; Glanz, Hunter; Piccolo, Brian D.; Abo-Ismail, Mohammed; Frano, Michael R. La; Manjarín, Rodrigo

doi:10.3390/brainsci12091193

Cited by 5 publications

(4 citation statements)

References 114 publications

(152 reference statements)

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“…Accumulated evidence indicates an association between NAFLD and neuro-pathologies, impacting both cognitive function and brain volume. Animal studies have demonstrated NAFLD effects on thalamic energy metabolism and hippocampal structure [6,9,49]. We used genetic tools for liver fat and liver volume to represent the liver health status in NAFLD [28,29].…”

Section: Discussionmentioning

confidence: 99%

“…NAFLD affects the central nervous system (CNS) via a variety of mechanisms, including metabolic disruptions, blood-brain barrier impairment, systemic inflammation, gut microbiota imbalances, and bile acid abnormalities [4,8]. One study found specific dietary interventions with certain oils could regulate the expression of some genes to preserve neuron quantity and synaptic density in a porcine model of NAFLD [9]. Neurodegenerative diseases often involve neuronal loss and abnormalities in cortical structure, identifiable through T1-weighted MRI [10,11].…”

Section: Introductionmentioning

confidence: 99%

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Bidirectional two-sample mendelian randomization analysis identifies causal associations of MRI-based cortical thickness and surface area relation to NAFLD

Mao,

Gao,

et al. 2024

Lipids Health Dis

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Background Non-alcoholic fatty liver disease (NAFLD) patients have exhibited extra-hepatic neurological changes, but the causes and mechanisms remain unclear. This study investigates the causal effect of NAFLD on cortical structure through bidirectional two-sample Mendelian randomization analysis. Methods Genetic data from 778,614 European individuals across four NAFLD studies were used to determine genetically predicted NAFLD. Abdominal MRI scans from 32,860 UK Biobank participants were utilized to evaluate genetically predicted liver fat and volume. Data from the ENIGMA Consortium, comprising 51,665 patients, were used to evaluate the associations between genetic susceptibility, NAFLD risk, liver fat, liver volume, and alterations in cortical thickness (TH) and surface area (SA). Inverse-variance weighted (IVW) estimation, Cochran Q, and MR-Egger were employed to assess heterogeneity and pleiotropy. Results Overall, NAFLD did not significantly affect cortical SA or TH. However, potential associations were noted under global weighting, relating heightened NAFLD risk to reduced parahippocampal SA and decreased cortical TH in the caudal middle frontal, cuneus, lingual, and parstriangularis regions. Liver fat and volume also influenced the cortical structure of certain regions, although no Bonferroni-adjusted p-values reached significance. Two-step MR analysis revealed that liver fat, AST, and LDL levels mediated the impact of NAFLD on cortical structure. Multivariable MR analysis suggested that the impact of NAFLD on the cortical TH of lingual and parstriangularis was independent of BMI, obesity, hyperlipidemia, and diabetes. Conclusion This study provides evidence that NAFLD causally influences the cortical structure of the brain, suggesting the existence of a liver-brain axis in the development of NAFLD.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Bidirectional two-sample mendelian randomization analysis identifies causal associations of MRI-based cortical thickness and surface area relation to NAFLD

Mao,

Gao,

et al. 2024

Lipids Health Dis

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“…Metabolomic data was analyzed using the %polynova_1way SAS macro [33]. Transcriptomic data were analyzed using a generalized linear model with an assumption of a negative binomial distribution of gene counts and using a 5% FDR threshold in edgeR-Bioconductor packageBio package" as previously described [34]. The Database for Annotation, Visualization, and Integrated Discovery (DAVID) software version 6.8 [35] was used to perform functional enrichment analyses on differently expressed genes.…”

Section: Methodsmentioning

confidence: 99%

Decreased FXR Agonism in the Bile Acid Pool Is Associated with Impaired FXR Signaling in a Pig Model of Pediatric NAFLD

Maj,

Burrin,

Manjarín

2023

Biomedicines

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The objective of this study was to investigate whether the impairment of farnesoid X receptor (FXR)-fibroblast growth factor 19 (FGF19) signaling in juvenile pigs with non-alcoholic fatty liver disease (NAFLD) is associated with changes in the composition of the enterohepatic bile acid pool. Eighteen 15-day-old Iberian pigs, pair-housed in pens, were allocated to receive either a control (CON) or high-fructose, high-fat (HFF) diet. Animals were euthanized in week 10, and liver, blood, and distal ileum (DI) samples were collected. HFF-fed pigs developed NAFLD and had decreased FGF19 expression in the DI and lower FGF19 levels in the blood. Compared with the CON, the HFF diet increased the total cholic acid (CA) and the CA to chenodeoxycholic acid (CDCA) ratio in the liver, DI, and blood. CA and CDCA levels in the DI were negatively and positively correlated with ileal FGF19 expression, respectively, and blood levels of FGF19 decreased with an increasing ileal CA to CDCA ratio. Compared with the CON, the HFF diet increased the gene expression of hepatic 12-alpha-hydrolase, which catalyzes the synthesis of CA in the liver. Since CA species are weaker FXR ligands than CDCA, our results suggest that impairment of FXR-FGF19 signaling in NAFLD pigs is associated with a decrease in FXR agonism in the bile acid pool.

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“…The results included improvements in various biochemical markers related to inflammation and brain function, suggesting potential neuroprotective effects. [197] Olive oil…”

Section: Molecular Effectsmentioning

confidence: 99%

Neuroprotective Effects of Olive Oil: A Comprehensive Review of Antioxidant Properties

Gonçalves,

Vale,

Silva

2024

Antioxidants

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Neurodegenerative diseases are a significant challenge to global healthcare, and oxidative stress plays a crucial role in their development. This paper presents a comprehensive analysis of the neuroprotective potential of olive oil, with a primary focus on its antioxidant properties. The chemical composition of olive oil, including key antioxidants, such as oleuropein, hydroxytyrosol, and oleocanthal, is systematically examined. The mechanisms by which these compounds provide neuroprotection, including counteracting oxidative damage and modulating neuroprotective pathways, are explored. The neuroprotective efficacy of olive oil is evaluated by synthesizing findings from various sources, including in vitro studies, animal models, and clinical trials. The integration of olive oil into dietary patterns, particularly its role in the Mediterranean diet, and its broader implications in neurodegenerative disease prevention are also discussed. The challenges in translating preclinical findings to clinical applications are acknowledged and future research directions are proposed to better understand the potential of olive oil in mitigating the risk of neurodegenerative conditions. This review highlights olive oil not only as a dietary component, but also as a promising candidate in preventive neurology, advocating for further investigation in the context of neurodegenerative diseases.

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Olive- and Coconut-Oil-Enriched Diets Decreased Secondary Bile Acids and Regulated Metabolic and Transcriptomic Markers of Brain Injury in the Frontal Cortexes of NAFLD Pigs

Cited by 5 publications

References 114 publications

Bidirectional two-sample mendelian randomization analysis identifies causal associations of MRI-based cortical thickness and surface area relation to NAFLD

Bidirectional two-sample mendelian randomization analysis identifies causal associations of MRI-based cortical thickness and surface area relation to NAFLD

Decreased FXR Agonism in the Bile Acid Pool Is Associated with Impaired FXR Signaling in a Pig Model of Pediatric NAFLD

Neuroprotective Effects of Olive Oil: A Comprehensive Review of Antioxidant Properties

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