High uric acid induced hippocampal mitochondrial dysfunction and cognitive impairment involving intramitochondrial NF-κB inhibitor α/nuclear factor-κB pathway

Shi, Chun; Guo, Hong-Fen; Liu, Xintong

doi:10.1097/wnr.0000000000001762

Cited by 6 publications

(2 citation statements)

References 21 publications

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“…Consistent with the hypothesis that decreased intracellular ATP is an important trigger involved in obesity and the metabolic syndrome, low ATP can be induced in a variety of cell types and tissues by fructose [16,58–61], as well as by uric acid [12,43,44,62]. Fructose-induced ATP depletion in the liver can be partially reversed by allopurinol [45].…”

Section: Fructose Triggers the Survival Switch By Lowering Atp Levelsmentioning

confidence: 77%

The fructose survival hypothesis for obesity

Johnson

Lanaspa

Sánchez-Lozada

et al. 2023

Phil. Trans. R. Soc. B

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The fructose survival hypothesis proposes that obesity and metabolic disorders may have developed from over-stimulation of an evolutionary-based biologic response (survival switch) that aims to protect animals in advance of crisis. The response is characterized by hunger, thirst, foraging, weight gain, fat accumulation, insulin resistance, systemic inflammation and increased blood pressure. The process is initiated by the ingestion of fructose or by stimulating endogenous fructose production via the polyol pathway. Unlike other nutrients, fructose reduces the active energy (adenosine triphosphate) in the cell, while blocking its regeneration from fat stores. This is mediated by intracellular uric acid, mitochondrial oxidative stress, the inhibition of AMP kinase and stimulation of vasopressin. Mitochondrial oxidative phosphorylation is suppressed, and glycolysis stimulated. While this response is aimed to be modest and short-lived, the response in humans is exaggerated due to gain of ‘thrifty genes’ coupled with a western diet rich in foods that contain or generate fructose. We propose excessive fructose metabolism not only explains obesity but the epidemics of diabetes, hypertension, non-alcoholic fatty liver disease, obesity-associated cancers, vascular and Alzheimer's dementia, and even ageing. Moreover, the hypothesis unites current hypotheses on obesity. Reducing activation and/or blocking this pathway and stimulating mitochondrial regeneration may benefit health-span. This article is part of a discussion meeting issue ‘Causes of obesity: theories, conjectures and evidence (Part I)’.

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Section: Fructose Triggers the Survival Switch By Lowering Atp Levelsmentioning

confidence: 77%

The fructose survival hypothesis for obesity

Johnson

Lanaspa

Sánchez-Lozada

et al. 2023

Phil. Trans. R. Soc. B

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“…As part of the purine degradation pathway, the last product of AMP metabolism via AMPD in humans is uric acid. 22 , 30 Even though uric acid has antioxidant properties, high uric acid levels have been associated with inflammation, oxidative stress, and mitochondrial dysfunction 31 , 32 , 33 , 34 , 35 , 36 , and correlate with the severity of kidney disease 37 , 38 , 39 and sarcopenia. 40 Consistently, urate lowering therapies like the use of xanthine oxidase inhibitors reduce sarcopenia in dialysis patients.…”

Section: Introductionmentioning

confidence: 99%

Phosphate depletion in insulin-insensitive skeletal muscle drives AMPD activation and sarcopenia in chronic kidney disease

Andrés-Hernando¹,

Cicerchi²,

García³

et al. 2023

iScience

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Role of uric acid in neurodegenerative diseases, focusing on Alzheimer and Parkinson disease: A new perspective

Alrouji,

Al‐kuraishy,

Al‐Gareeb

et al. 2024

Neuropsychopharm Rep

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Neurodegenerative diseases (NDs) such as Alzheimer disease (AD) and Parkinson disease (PD) are group of diseases affecting the central nervous system (CNS) characterized by progressive neurodegenerations and cognitive impairment. Findings from different studies highlighted the beneficial and detrimental effects of serum uric acid on the development and progression of NDs. Therefore, this mini‐review aims to discuss the beneficial and detrimental effects of uric on NDs. The neuroprotective effect of uric acid is mainly related to the antioxidant effect of uric acid which alleviates oxidative stress‐induced neurodegeneration in AD and PD. However, long‐term effect of hyperuricemia prompts for the development and progression of cognitive impairment. Hyperuricemia is associated with cognitive impairment and dementia, and gout increases dementia risk. In addition, hyperuricemia can cause cerebral vascular injury which is a risk factor for vascular dementia and cognitive impairment. Taken together, the relationship between uric acid and NDs risk remains conflicting. Hence, preclinical and clinical studies are indicated in this regard.

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High uric acid induced hippocampal mitochondrial dysfunction and cognitive impairment involving intramitochondrial NF-κB inhibitor α/nuclear factor-κB pathway

Cited by 6 publications

References 21 publications

The fructose survival hypothesis for obesity

The fructose survival hypothesis for obesity

Phosphate depletion in insulin-insensitive skeletal muscle drives AMPD activation and sarcopenia in chronic kidney disease

Role of uric acid in neurodegenerative diseases, focusing on Alzheimer and Parkinson disease: A new perspective

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