β-Hydroxybutyrate Prevents Vascular Senescence through hnRNP A1-Mediated Upregulation of Oct4

Han, Young‐Min; Bédarida, Tatiana; Ding, Ye; Somba, Brian K.; Lu, Qiulun; Wang, Qilong; Song, Ping

doi:10.1016/j.molcel.2018.07.036

Cited by 105 publications

(84 citation statements)

References 52 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Cellular senescence of endothelial cells and VSMCs are observed in vascular diseases such as atherosclerosis and arterial aneurysm [11,140,141]. β-hydroxybutyrate suppresses vascular senescence by enhancing the expression of the transcription factor OCT4, which could increase Lamin B1, a pivotal factor against DNA damage-induced senescence [142]. Activation of GPR109A by β-hydroxybutyrate induces an anti-inflammatory phenotype of monocytes/macrophages that depends on prostaglandin D2 (PGD2) production by cyclooxygenase 1 (COX1) and the hematopoietic PGD2 synthase (HPGDS) [143].…”

Section: Butyrate and Butyrylationmentioning

confidence: 99%

Short-chain fatty acid, acylation and cardiovascular diseases

2020

View full text Add to dashboard Cite

Cardiovascular diseases (CVDs) are the leading cause of morbidity and mortality worldwide. Metabolic dysfunction is a fundamental core mechanism underlying CVDs. Previous studies generally focused on the roles of long-chain fatty acids (LCFAs) in CVDs. However, a growing body of study has implied that short-chain fatty acids (SCFAs: namely propionate, malonate, butyrate, 2-hydroxyisobutyrate (2-HIBA), β-hydroxybutyrate, crotonate, succinate, and glutarate) and their cognate acylations (propionylation, malonylation, butyrylation, 2-hydroxyisobutyrylation, β-hydroxybutyrylation, crotonylation, succinylation, and glutarylation) participate in CVDs. Here, we attempt to provide an overview landscape of the metabolic pattern of SCFAs in CVDs. Especially, we would focus on the SCFAs and newly identified acylations and their roles in CVDs, including atherosclerosis, hypertension, and heart failure. Clinical Science (2020) 134 657-676 https://doi.org/10.1042/CS20200128 cofactors in certain protein acylations, such as propionylation [14], malonylation [15], butyrylation [14], 2-hydroxyisobutyrylation [16], β-hydroxybutyrylation [17], crotonylation [18], succinylation [19], and glutarylation [20]. These discoveries give us a deeper understanding of PTM. Among PTMs, protein acetylation is the earliest discovered and most studied. Similar to protein acetylation, various studies have shown that these newly discovered PTMs are also involved in physiological and pathophysiological processes, including cardiovascular homeostasis.Here in this review, we will summarize SCFAs, protein acylations, and their emerging roles in CVDs, including atherosclerosis, hypertension, and heart failure. The metabolic pattern and FAs in CVDsThe heart is an 'omnivore' , using FAs, glucose, lactate, ketone bodies, and amino acids as metabolic substrates [5,6]. The substrates utilized by the embryonic heart are significantly different from those used by the adult heart. The embryonic heart depends primarily on glycolysis as well as lactate oxidation to produce energy [21]. The newborn and adult heart shift toward the remarkable utilization of FAs to meet cardiac energy demand [5,9]. In failing hearts, a decrease in FA oxidation and an increase in glycolysis are critically involved in cardiac dysfunction [22]. As thus, the metabolic pattern is essential for maintaining cardiac and vascular functions.Diabetes, hypertension, and obesity contribute to heart failure syndrome. Accumulating evidence suggests that hypertension, ischemic hearts, and heart failure induce a shift in substrate toward the remarkable utilization of glucose to generate energy. Despite this shift, the FA oxidation remains to make much energy for the diseased heart [23]. Since FAs are the predominant substrates for cardiomyocytes, alterations in FA metabolism have been implicated as causal in cardiac diseases. FAs within cells and in the circulation are critically involved in cardiometabolic diseases. CVDs are closely associated with lifestyle and metabolic status, which affect circul...

show abstract

Section: Butyrate and Butyrylationmentioning

confidence: 99%

Short-chain fatty acid, acylation and cardiovascular diseases

2020

View full text Add to dashboard Cite

show abstract

“…Upregulation of circulating β-HB delays the aging progress of mice by preventing vascular cell senescence. In addition, hnRNP A1 antagonized cellular senescence and SASP via stabilization of Oct4 and Sirt1 mRNAs 15,73 . In addition, a constitutive decrease in the levels and activities of hnRNP A1 or A2 in senescent fibroblasts is typically accompanied by an increase in the level of the p16 (INK4a) isoform, which is a primary aging marker 74 .…”

Section: Rna-binding Proteinsmentioning

confidence: 99%

“…Indeed, β-HB supplementation extends the lifespan of C. elegans by 20% through the DAF-16/FOXO and SKN-1/Nrf pathways and the regulation of aging and longevity 14 . In mammals, β-HB decreases the senescenceassociated secretory phenotype (SASP) and the senescence of vascular cells 15 . Moreover, the ketogenic diet significantly extended the median lifespan of mice and resulted in the preservation of the physical function of aged mice 13 .…”

Section: Agingmentioning

confidence: 99%

“…β-HB directly binds several RNA-binding proteins, including heterogeneous nuclear ribonucleoprotein A1 (hnRNP A1), splicing factor proline and glutamine rich (SFPQ), and RNA-binding protein FUS/TLS. hnRNP A1 is a dominant binding partner of β-HB in vascular cells, such as endothelial and smooth muscle cells 15 . Upregulation of circulating β-HB delays the aging progress of mice by preventing vascular cell senescence.…”

Section: Rna-binding Proteinsmentioning

confidence: 99%

See 1 more Smart Citation

β-hydroxybutyrate and its metabolic effects on age-associated pathology

2020

Self Cite

View full text Add to dashboard Cite

Aging is a universal process that renders individuals vulnerable to many diseases. Although this process is irreversible, dietary modulation and caloric restriction are often considered to have antiaging effects. Dietary modulation can increase and maintain circulating ketone bodies, especially β-hydroxybutyrate (β-HB), which is one of the most abundant ketone bodies in human circulation. Increased β-HB has been reported to prevent or improve the symptoms of various age-associated diseases. Indeed, numerous studies have reported that a ketogenic diet or ketone ester administration alleviates symptoms of neurodegenerative diseases, cardiovascular diseases, and cancers. Considering the potential of β-HB and the intriguing data emerging from in vivo and in vitro experiments as well as clinical trials, this therapeutic area is worthy of attention. In this review, we highlight studies that focus on the identified targets of β-HB and the cellular signals regulated by β-HB with respect to alleviation of age-associated ailments.

show abstract

“…Although the mechanism underlying the anti-aging effects of ketone bodies has not been fully elucidated, recent studies provided strong evidences supporting their anti-inflammatory [32] and anti-oxidative effects [33,34]. Thus, prevention of senescence by BHB has been demonstrated in vascular cells [35]. Ketone bodies can modulate inflammatory and immune cell function.…”

Section: Physiological Homeostasismentioning

confidence: 99%

More Than One HMG-CoA Lyase: The Classical Mitochondrial Enzyme Plus the Peroxisomal and the Cytosolic Ones

Arnedo

Latorre‐Pellicer

Lucia-Campos

et al. 2019

IJMS

View full text Add to dashboard Cite

There are three human enzymes with HMG-CoA lyase activity that are able to synthesize ketone bodies in different subcellular compartments. The mitochondrial HMG-CoA lyase was the first to be described, and catalyzes the cleavage of 3-hydroxy-3-methylglutaryl CoA to acetoacetate and acetyl-CoA, the common final step in ketogenesis and leucine catabolism. This protein is mainly expressed in the liver and its function is metabolic, since it produces ketone bodies as energetic fuels when glucose levels are low. Another isoform is encoded by the same gene for the mitochondrial HMG-CoA lyase (HMGCL), but it is located in peroxisomes. The last HMG-CoA lyase to be described is encoded by a different gene, HMGCLL1, and is located in the cytosolic side of the endoplasmic reticulum membrane. Some activity assays and tissue distribution of this enzyme have shown the brain and lung as key tissues for studying its function. Although the roles of the peroxisomal and cytosolic HMG-CoA lyases remain unknown, recent studies highlight the role of ketone bodies in metabolic remodeling, homeostasis, and signaling, providing new insights into the molecular and cellular function of these enzymes.

show abstract

β-Hydroxybutyrate Prevents Vascular Senescence through hnRNP A1-Mediated Upregulation of Oct4

Cited by 105 publications

References 52 publications

Short-chain fatty acid, acylation and cardiovascular diseases

Short-chain fatty acid, acylation and cardiovascular diseases

β-hydroxybutyrate and its metabolic effects on age-associated pathology

More Than One HMG-CoA Lyase: The Classical Mitochondrial Enzyme Plus the Peroxisomal and the Cytosolic Ones

Contact Info

Product

Resources

About