ArticleAdvances in experimental medicine and biology2022
Chronic Ketosis Modulates HIF1α-Mediated Inflammatory Response in Rat Brain.
Article in Advances in experimental medicine and biology, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers.
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4 citing papers in PubMed, 9 citations in OpenAlex.
- Article
- Chronic Ketosis Provides Neuroprotection Through HIF- 1α-Mediated Control of the TXNIP/NLRP3 Axis by Regulating the Inflammatory and Apoptotic Response.Molecular neurobiology · 2025Article
- Effects of Ketogenic Diet on Increased Ethanol Consumption Induced by Social Stress in Female Mice.Nutrients · 2024Article
- Nutritional strategies cause memory damage and alter biochemical parameters without causing neuroinflammation.Metabolic brain disease · 2024Article
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Authors and funding
6 authors at 2 institutions in 1 country.
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No grant is acknowledged in the PubMed record.
Abstract
Hypoxia inducible factor alpha (HIF1α) is associated with neuroprotection conferred by diet-induced ketosis but the underlying mechanism remains unclear. In this study we use a ketogenic diet in rodents to induce a metabolic state of chronic ketosis, as measured by elevated blood ketone bodies. Chronic ketosis correlates with neuroprotection in both aged and following focal cerebral ischaemia and reperfusion (via middle cerebral artery occlusion, MCAO) in mouse and rat models. Ketone bodies are known to be used efficiently by the brain and metabolism of ketone bodies is associated with increased cytosolic succinate levels that inhibits prolyl hydroxylases allowing HIF1α to accumulate. Ketosis also regulates inflammatory pathways, and HIF1α is reported to be essential for gene expression of interleukin10 (IL10). Therefore we hypothesised that ketosis-stabilised HIF1α modulates the expression of inflammatory cytokines orchestrating neuroprotection. To test changes in cytokine levels in rodent brain, eight-week-old rats were fed either the standard chow diet (SD) or the ketogenic (KG) diet for 4 weeks before ischaemia experiments (MCAO) were performed and the brain tissues were collected. Consistent with our hypothesis, immunoblotting analysis shows IL10 levels were significantly higher in KG diet rat brain compared to SD, whereas the TNFα and IL6 levels were significantly lower in the brains of KG diet fed group.
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