β-hydroxybutyrate Impedes the Progression of Alzheimer’s Disease and Atherosclerosis in ApoE-Deficient Mice

Krishnan, Manigandan; Hwang, Jong Su; Kim, Mi-Kyung; Kim, Yun Jin; Seo, Ji Hae; Jung, Jeeyoun; Ha, Eunyoung

doi:10.3390/nu12020471

Cited by 26 publications

(22 citation statements)

References 44 publications

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“…However, there are many experimental and clinical studies providing evidence that ketone bodies, especially BHB, have treatment effects for atherosclerosis. So far, many studies have reported that ketone bodies can reduce insulin resistance and serum resistin levels, which is a proven risk factor for atherosclerosis [ 54 , 55 ]. In addition, because of its molecular mechanisms, some studies have found that BHB can attenuate atherosclerosis via the GPR109A–NLRP3 pathway.…”

Section: Discussionmentioning

confidence: 99%

Exercise Ameliorates Atherosclerosis via Up-Regulating Serum β-Hydroxybutyrate Levels

Zong-ze

Zhang

et al. 2022

IJMS

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Atherosclerosis, accompanied by inflammation and metabolic disorders, is the primary cause of clinical cardiovascular death. In recent years, unhealthy lifestyles (e.g., sedentary lifestyles) have contributed to a worldwide epidemic of atherosclerosis. Exercise is a known treatment of atherosclerosis, but the precise mechanisms are still unknown. Here, we show that 12 weeks of regular exercise training on a treadmill significantly decreased lipid accumulation and foam cell formation in ApoE−/− mice fed with a Western diet, which plays a critical role in the process of atherosclerosis. This was associated with an increase in β-hydroxybutyric acid (BHB) levels in the serum. We provide evidence that BHB treatment in vivo or in vitro increases the protein levels of cholesterol transporters, including ABCA1, ABCG1, and SR-BI, and is capable of reducing lipid accumulation. It also ameliorated autophagy in macrophages and atherosclerosis plaques, which play an important role in the step of cholesterol efflux. Altogether, an increase in serum BHB levels after regular exercise is an important mechanism of exercise inhibiting the development of atherosclerosis. This provides a novel treatment for atherosclerotic patients who are unable to undertake regular exercise for whatever reason. They will gain a benefit from receiving additional BHB.

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Section: Discussionmentioning

confidence: 99%

Exercise Ameliorates Atherosclerosis via Up-Regulating Serum β-Hydroxybutyrate Levels

Zong-ze

Zhang

et al. 2022

IJMS

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“… 47 On the other hand, studies have shown that exogenous 2-hydroxybutanoic acid has therapeutic benefits against stress conditions, such as kidney injury, 48 depression, 49 Alzheimer’s disease, and atherosclerosis. 50 Further studies are warranted to discover the precise function of 2-hydroxybutanoic acid in asthma.…”

Section: Discussionmentioning

confidence: 99%

<p>Urinary Metabolomic Profiling Reveals Biological Pathways and Predictive Signatures Associated with Childhood Asthma</p>

Liu

Zhou

et al. 2020

JAA

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Background Despite considerable efforts, the pathogenic mechanisms of asthma are still incompletely understood, due to its heterogeneous nature. However, metabolomics can offer a global view of a biological system, making it a valuable tool for further elucidation of mechanisms and biomarker discovery in asthma. Methods GC-MS–based metabolomic analysis was conducted for comparison of urine metabolic profiles between asthmatic children (n=30) and healthy controls (n=30). Results An orthogonal projections to latent structures discriminant–analysis model revealed a clear separation of the asthma and control groups ( R 2 x =0.137, R 2 y =0.947, Q 2 =0.82). A total of 20 differential metabolites were identified as discriminant factors, of which eleven were significantly increased and nine decreased in the asthma group compared to the control group. Pathway-enrichment analysis based on these differential metabolites indicated that sphingolipid metabolism, protein biosynthesis, and citric acid cycle were strongly associated with asthma. Among the identified metabolites, 2-hydroxybutanoic acid showed excellent discriminatory performance for distinguishing asthma from healthy controls, with an AUC of 0.969. Conclusion Our study revealed significant changes in the urine metabolome of asthma patients. Several perturbed pathways (eg, sphingolipid metabolism and citric acid cycle) may be related to asthma pathogenesis, and 2-hydroxybutanoic acid could serve as a potential biomarker for asthma diagnosis.

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“…To date, there is only one study that measured the effect of the ketone body, β-hydroxybutyrate (a known by-product of fasting), on tau tangles. The study demonstrated a reduction in high-fat diet (HFD)-induced aggregates of tau tangles in apolipoproteinE4 (APOE4)-deficient mice following its administration [ 62 ]. This provides promising proof that the application of intermittent fasting is highly relevant when using an appropriate model.…”

Section: Discussionmentioning

confidence: 99%

Studying the Relationship of Intermittent Fasting and β-Amyloid in Animal Model of Alzheimer’s Disease: A Scoping Review

2020

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We examined the evidence for intermittent fasting (IF) as a preventative tool to influence β-amyloid in animal models of Alzheimer’s disease (AD). A Scopus, Ovid, PubMed, and Web of Science (WoS), search yielded 29 results using the keywords “amyloid beta”, “intermittent fasting”, “intermittent caloric restriction”, “alternate day fasting”, “modified alternate-day fasting”, “time-restricted feeding”, “Ramadan fast”, “intermittent calori* restriction”, “intermittent restrictive diet”, and “Alzheimer*”. Five research articles addressed directly the effects of intermittent fasting on β-amyloid levels in animal models of AD: alternate day fasting (ADF) and time-restricted feeding (TRF) methods were incorporated in these studies. The study designs were found to be heterogeneous. Variations in the levels of β-amyloid peptides or plaque in either the hippocampus, cortical areas, or both in animals following dietary intervention were observed as compared to the ad libitum group. Non-significant changes were observed in three studies, while two studies interestingly demonstrated amelioration and reduction in β-amyloid levels. Given the conflicting results obtained from this study, significant care has to be taken into consideration before the protocol can be applied as a preventative approach to treat Alzheimer’s disease. Longitudinal research is warranted to fully grasp how dietary habits can help alleviate the disease either through upstream or downstream of AD pathology.

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β-hydroxybutyrate Impedes the Progression of Alzheimer’s Disease and Atherosclerosis in ApoE-Deficient Mice

Cited by 26 publications

References 44 publications

Exercise Ameliorates Atherosclerosis via Up-Regulating Serum β-Hydroxybutyrate Levels

Exercise Ameliorates Atherosclerosis via Up-Regulating Serum β-Hydroxybutyrate Levels

<p>Urinary Metabolomic Profiling Reveals Biological Pathways and Predictive Signatures Associated with Childhood Asthma</p>

Studying the Relationship of Intermittent Fasting and β-Amyloid in Animal Model of Alzheimer’s Disease: A Scoping Review

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