Fatty Acid Binding Protein 3 (FABP3) and Apolipoprotein E4 (ApoE4) as Lipid Metabolism-Related Biomarkers of Alzheimer’s Disease

Dulewicz, Maciej; Kulczyńska-Przybik, Agnieszka; Słowik, Agnieszka; Borawska, Renata; Mroczko, Barbara

doi:10.3390/jcm10143009

Cited by 13 publications

(12 citation statements)

References 69 publications

(167 reference statements)

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“…FABP1 is a liver-specific fatty acid-binding protein that plays important roles in intracellular lipid metabolism in the liver, and the knockdown of FABP1 in liver decreased the liver weight and hepatic TG (51). FABP3 seems to be lipid metabolism-related biomarker in Alzheimer's disease (52). Markedly, increase in FABP3 mRNA expression in rats' livers and adipose tissue was reported with high-cholesterol diet (53).…”

Section: Discussionmentioning

confidence: 99%

Instant Dark Tea Alleviates Hyperlipidaemia in High-Fat Diet-Fed Rat: From Molecular Evidence to Redox Balance and Beyond

Qin

Yuanjie³

et al. 2022

Front. Nutr.

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Instant dark tea (IDT) is a new product gaining increasing attention because it is convenient and can endow significant health benefit to consumers, which is partially attributed to its high concentration of functional ingredients. However, the molecular mechanism underlying its regulatory effect on hyperlipidaemia is rarely studied. In this study, we performed omics and molecular verification in high-fat diet (HFD)-fed rat, aiming to reveal the mechanism and provide molecular evidence. The results showed that the major bioactive components in IDT were 237.9 mg/g total polysaccharides, 336.6 mg/g total polyphenols, and 46.9 mg/g EGCG. Rats fed with IDT (0.27–0.54 g/kg for 12 weeks) significantly reduced the body weight and TC, TG, LDL-C, blood glucose, and MDA and induced the level of serum HDL-C and also the levels of liver SOD, CAT, GSH-Px, and Nrf2, compared to HFD group. For molecular mechanism study, HIDT feeding had significant impact on the gene expressions of biomarkers in lipogenesis (FABP, CD36, SCD1, Cyp4a1, and Kcnn2), lipid oxidation (PPARγ), and glucose glycolysis (Gck and ENO2) in liver tissue. Moreover, gut microbiome study found that rats fed with IDT dramatically modified the gut microbial species at the family level, such as suppressing the increase abundance of Proteobacteria and Firmicutes induced by HFD. HIDT significantly boosted the relative composition of beneficial bacterium Akkermansia and Rikenellaceae_RC9_gut_group and decreased the relative abundance of the harmful bacterium Ruminococcaceae_UCG-005 and Ruminiclostridium_9, compared to HFD (p < 0.01). Correlation analysis between microbiome and animal indicators found that seven genera including Akkermansia, Clostridiales, Lachnospiraceae, Lachnospiraceae_UCG-010, Ruminiclostridium_9, Ruminococaceae-UCG-005, and Ruminocuccus_1 were found as potential biomarkers that were strongly correlated with oxidative stress and metabolism genes. For instance, Ruminococcaceae_UCG-005 was significantly correlated with body weight, TG, HDL-C, Nfr2, FABP3, SCD1, Cyp4a1, and Kcnn2. Collectively, the above data obtained in this study had provided the primary molecular evidence for the molecular mechanism and brought in novel insights based on omics for the regulatory effect of IDT on hyperlipidaemia.

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Section: Discussionmentioning

confidence: 99%

Instant Dark Tea Alleviates Hyperlipidaemia in High-Fat Diet-Fed Rat: From Molecular Evidence to Redox Balance and Beyond

Qin

Yuanjie³

et al. 2022

Front. Nutr.

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“…In addition to its role in PD, FABP3 is also considered a marker of AD because of its relation with Aβ accumulation [ 86 ]. It was even proposed that FABP3 negatively correlates with the severity of the disease: a large amount of FABP3 was detected in the CSF of AD brains, suggesting its correlation with neurodegenerative processes [ 87 ]. In this regard, considering that FABP3 is primarily found in gray matter, its location in the CSF is uncommon and reflects destructive processes that occur in neuronal membrane lipids [ 88 ].…”

Section: Fatty Acid Binding Proteins In Neurodegenerationmentioning

confidence: 99%

Exploring the Role of Lipid-Binding Proteins and Oxidative Stress in Neurodegenerative Disorders: A Focus on the Neuroprotective Effects of Nutraceutical Supplementation and Physical Exercise

et al. 2022

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The human brain is primarily composed of lipids, and their homeostasis is crucial to carry on normal neuronal functions. In order to provide an adequate amount of lipid transport in and out of the central nervous system, organisms need a set of proteins able to bind them. Therefore, alterations in the structure or function of lipid-binding proteins negatively affect brain homeostasis, as well as increase inflammation and oxidative stress with the consequent risk of neurodegeneration. In this regard, lifestyle changes seem to be protective against neurodegenerative processes. Nutraceutical supplementation with antioxidant molecules has proven to be useful in proving cognitive functions. Additionally, regular physical activity seems to protect neuronal vitality and increases antioxidant defenses. The aim of the present review was to investigate mechanisms that link lipid-binding protein dysfunction and oxidative stress to cognitive decline, also underlining the neuroprotective effects of diet and exercise.

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“…Previous studies found that CSF levels of HFABP in AD patients were higher than in MCI subjects and older people without cognition impairment (Chiasserini et al, 2017;Höglund et al, 2017;Dulewicz et al, 2021). Furthermore, other studies found significantly elevated CSF HFABP levels have been described in MCI subjects compared with the cognitively healthy group, but no difference between the dementia group and the progressive MCI subgroup (Guo et al, 2013).…”

Section: Discussionmentioning

confidence: 91%

Heart fatty acid-binding protein is associated with phosphorylated tau and longitudinal cognitive changes

Wang

Huang

et al. 2022

Front. Aging Neurosci.

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BackgroundPerturbation of lipid metabolism is associated with Alzheimer’s disease (AD). Heart fatty acid-binding protein (HFABP) is an adipokine playing an important role in lipid metabolism regulation.Materials and methodsTwo datasets separately enrolled 303 and 197 participants. First, we examine the associations of cerebrospinal fluid (CSF) HFABP levels with cognitive measures [including Mini-Mental State Examination (MMSE), Clinical Dementia Rating sum of boxes (CDRSB), and the cognitive section of Alzheimer’s Disease Assessment Scale] and AD biomarkers (CSF amyloid beta and tau levels). Second, we examine the longitudinal associations of baseline CSF HFABP levels and the variability of HFABP with cognitive measures and AD biomarkers. Structural equation models explored the mediation effects of AD pathologies on cognition.ResultsWe found a significant relationship between CSF HFABP level and P-tau (dataset 1: β = 2.04, p < 0.001; dataset 2: β = 1.51, p < 0.001). We found significant associations of CSF HFABP with longitudinal cognitive measures (dataset 1: ADAS13, β = 0.09, p = 0.008; CDRSB, β = 0.10, p = 0.003; MMSE, β = −0.15, p < 0.001; dataset 2: ADAS13, β = 0.07, p = 0.004; CDRSB, β = 0.07, p = 0.005; MMSE, β = −0.09, p < 0.001) in longitudinal analysis. The variability of HFABP was associated with CSF P-tau (dataset 2: β = 3.62, p = 0.003). Structural equation modeling indicated that tau pathology mediated the relationship between HFABP and cognition.ConclusionOur findings demonstrated that HFABP was significantly associated with longitudinal cognitive changes, which might be partially mediated by tau pathology.

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Fatty Acid Binding Protein 3 (FABP3) and Apolipoprotein E4 (ApoE4) as Lipid Metabolism-Related Biomarkers of Alzheimer’s Disease

Cited by 13 publications

References 69 publications

Instant Dark Tea Alleviates Hyperlipidaemia in High-Fat Diet-Fed Rat: From Molecular Evidence to Redox Balance and Beyond

Instant Dark Tea Alleviates Hyperlipidaemia in High-Fat Diet-Fed Rat: From Molecular Evidence to Redox Balance and Beyond

Exploring the Role of Lipid-Binding Proteins and Oxidative Stress in Neurodegenerative Disorders: A Focus on the Neuroprotective Effects of Nutraceutical Supplementation and Physical Exercise

Heart fatty acid-binding protein is associated with phosphorylated tau and longitudinal cognitive changes

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