Protective action of the microbial metabolite butyrate against cardiomyocyte hypertrophy

2020 ◽  
Vol 41 (Supplement_2) ◽  
Author(s):  
M Umei ◽  
H Akazawa ◽  
A Saga-Kamo ◽  
H Yagi ◽  
Q Liu ◽  
...  
Keyword(s):  
Heart Failure ◽  
Short Chain Fatty Acid ◽  
Short Chain Fatty Acids ◽  
Chain Fatty Acid ◽  
G Protein Coupled Receptors ◽  
Short Chain ◽  
Cardiomyocyte Hypertrophy ◽  
Cell Transcriptome ◽  
Single Cell Transcriptome ◽  
G Protein Coupled

Abstract Introduction Short-chain fatty acids are one of the gut microbial metabolites that may influence host physiology. We previously reported that gut dysbiosis was associated with heart failure, and that the proportions of butyrate-producing bacteria diminished prominently in the gut of patients with heart failure. Purpose We investigated the molecular mechanism of butyrate and investigated the protective mechanism against heart failure. Methods We searched for G protein-coupled receptors for short-chain fatty acids using single-cell transcriptome analysis of cardiomyocytes and non-cardiomyocytes isolated from murine hearts. In addition, we examined the effects of butyrate on endothelin-1 (ET1) or isoproterenol-induced hypertrophic responses and histone deacetylase (HDAC) activities in cultured neonatal rat cardiomyocytes. Results Single-cell transcriptome analysis and co-expression network analysis revealed that G protein-coupled receptors for short-chain fatty acid receptors were not expressed in cardiomyocytes and that Olfr78 was expressed in vascular smooth muscle cells in the heart. Treatment with butyrate inhibited ET1-induced hypertrophic growth and up-regulation of the genes such as Nppa, Acta1, and Myh7 in cultured rat neonatal cardiomyocytes. Moreover, butyrate increased the acetylation levels of histone H3, indicating that butyrate has an inhibitory effect on HDAC in cardiomyocytes. In addition, treatment with butyrate caused up-regulation of Inpp5f, encoding inositol polyphosphate-5-phosphatase f, which was associated with a significant decrease in the phosphorylation levels of Akt. These results suggest that butyrate may act as HDAC inhibitor to increase Inpp5f gene expression, leading to the activation of Akt-glycogen synthase kinase 3beta (Gsk3beta) pathway, and thereby protect against hypertrophic responses. Conclusion There was no known GPCR for short-chain fatty acid expressed in cardiomyocytes. However, butyrate suppressed cardiomyocyte hypertrophy through epigenetic modification of gene expression. Our results may uncover a potential role of the dysbiosis of intestinal microbiota in the pathogenesis of cardiac hypertrophy and failure. Funding Acknowledgement Type of funding source: None

scholarly journals Peran mikrobiota usus dalam perkembangan obesitas

2019 ◽  
Vol 42 (1) ◽  
pp. 41
Author(s):  
Susmiati Susmiati
Keyword(s):  
Fatty Acid ◽  
G Protein ◽  
Short Chain Fatty Acid ◽  
Peptide Yy ◽  
Chain Fatty Acid ◽  
G Protein Coupled Receptors ◽  
Short Chain ◽  
G Protein Coupled

Sampai sekarang etiologi  obesitas masih belum jelas dan masih diperdebatkan. Baru-baru ini mikrobiota usus dianggap sebagai salah satu faktor yang berperan terhadap kejadian obesitas. Tujuan: Untuk membahas tentang peran mikrobiota usus terhadap kejadian obesitas. Metode: Artikel ini disusun berdasarkan review beberapa literature yang berhubungan dengan peran mikrobiota usus baik pada hewan coba maupun pada manusia dengan berbagai metode penelitian. Hasil: Pada penelusuran literature didapatkan  peran mikrobiota usus terhadap kejadian obesitas dapat melalui beberapa mekanisme yaitu melalui jalur metabolik, inflamasi dan hormonal. Jalur metabolik dengan peningkatan produksi Short-Chain Fatty Acid (SCFA), perubahan metabolisme asam empedu dan FXR/TGR5 signaling, jalur inflamasi dengan peningkatan lipopolisakarida (LPS) dan endocannabinoid (eCB) system yang mengatur metabolisme dan rasa lapar melalui microbiota-gut-brain axis serta jalur hormonal yaitu penekanan fiaf, peningkatan Peptide YY (PYY), dan ekspresi dari G protein coupled receptors (GPCRs). Simpulan: Beberapa penelitian menunjukkan mekanisme utama peran mikrobiota terhadap perkembangan obesitas dapat melalui jalur metabolik, inflamasi, maupun hormonal.

Abstract P320: The Gut Microbial Metabolite Butyrate Suppresses Cardiac Hypertrophy Via An Epigenetic Mechanism

2021 ◽  
Vol 129 (Suppl_1) ◽  
Author(s):  
Masahiko Umei ◽  
Hiroshi Akazawa ◽  
Akiko Saga-Kamo ◽  
Hiroki Yagi ◽  
Qing Liu ◽  
...  
Keyword(s):  
Heart Failure ◽  
Fatty Acid ◽  
Cardiac Hypertrophy ◽  
Short Chain Fatty Acid ◽  
Chain Fatty Acid ◽  
Epigenetic Mechanism ◽  
Neonatal Rat ◽  
Short Chain ◽  
Rat Cardiomyocytes ◽  
Hypertrophic Growth

Introduction: Short-chain fatty acids (SCFA) are one of the gut microbial metabolites that can influence host health and disease. We previously reported that gut dysbiosis is associated with heart failure, and that the proportion of butyrate-producing bacteria is decreased in the gut of patients with heart failure. Purpose: We investigated the molecular mechanism of butyrate in the development of cardiac hypertrophy. Methods and Results: Single-cell transcriptome analysis and co-expression network analysis revealed that G protein-coupled receptors for short-chain fatty acid receptors were not expressed in cardiomyocytes and that Olfr78 was expressed in vascular smooth muscle cells in the heart. On the other hand, treatment with butyrate inhibited ET1-induced and isoproterenol (ISO)-induced hypertrophic growth in cultured neonatal rat cardiomyocytes. Moreover, butyrate increased the acetylation levels of histone H3, suggesting the inhibitory effect of butyrate on HDAC. In addition, butyrate caused the degradation of HDAC2 and up-regulation of Inpp5f, encoding inositol polyphosphate-5-phosphatase f, leading to a significant decrease in the phosphorylation levels of Akt and glycogen synthase kinase 3β (GSK3β). Finally, intraperitoneal injection of butyrate inhibited ISO-induced cardiac hypertrophy in mice. These results suggest that butyrate protects against hypertrophic responses via suppression of the Akt-GSK3β pathway through HDAC inhibition. Conclusion: In the heart, there were no known short-chain fatty acid receptors in cardiomyocytes. However, butyrate was shown to have an epigenetic mechanism in suppressing effect on cardiomyocyte hypertrophy via suppression of HDAC2-Akt-GSK3β axis. Our results uncover a potential link between dysbiosis of intestinal microbiota and the development of cardiac hypertrophy.

scholarly journals Short Chain Fatty Acid Production from Mycoprotein and Mycoprotein Fibre in an In Vitro Fermentation Model

Nutrients ◽  
2019 ◽  
Vol 11 (4) ◽  
pp. 800 ◽  
Author(s):  
Hannah Harris ◽  
Christine Edwards ◽  
Douglas Morrison
Keyword(s):  
Energy Intake ◽  
Short Chain Fatty Acid ◽  
Short Chain Fatty Acids ◽  
Chain Fatty Acid ◽  
Fibre Content ◽  
Short Chain ◽  
Fatty Acid Production ◽  
In Vitro Fermentation ◽  
Fermentation Model

Dietary mycoprotein (marketed as QuornTM) has many health benefits, including reductions in energy intake. The majority of studies evaluating mycoprotein focus on the protein content and very few consider the fibre content. Fibre consumption is also associated with decreased energy intake, which is partly attributed to short chain fatty acids (SCFAs) from fibre fermentation by colonic bacteria. To study the SCFA-producing capability of mycoprotein, in vitro batch fermentations were conducted, and SCFA production compared with that from extracted mycoprotein fibre, oligofructose (OF), rhamnose, and laminarin. Mycoprotein and mycoprotein fibre were both fermentable, resulting in a total SCFA production of 24.9 (1.7) and 61.2 (15.7) mmol/L, respectively. OF led to a significantly higher proportion of acetate compared to all other substrates tested (92.6 (2.8)%, p < 0.01). Rhamnose generated the highest proportion of propionate (45.3 (2.0)%, p < 0.01), although mycoprotein and mycoprotein fibre yielded a higher proportion of propionate compared with OF and laminarin. Butyrate proportion was the highest with laminarin (28.0 (10.0)although mycoprotein fibre led to a significantly higher proportion than OF (p < 0.01). Mycoprotein is a valuable source of dietary protein, but its fibre content is also of interest. Further evaluation of the potential roles of the fibre content of mycoprotein is required.

scholarly journals Fecal Short-Chain Fatty Acid Concentrations Increase in Newly Paired Male Marmosets (Callithrix jacchus)

mSphere ◽  
2020 ◽  
Vol 5 (5) ◽  
Author(s):  
Lifeng Zhu ◽  
Mallory J. Suhr Van Haute ◽  
Haley R. Hassenstab ◽  
Caroline Smith ◽  
Devin J. Rose ◽  
...  
Keyword(s):  
Fatty Acids ◽  
Fatty Acid ◽  
Gut Microbiome ◽  
Short Chain Fatty Acid ◽  
Social Contact ◽  
Common Marmoset ◽  
Short Chain Fatty Acids ◽  
Chain Fatty Acid ◽  
Short Chain ◽  
Chain Fatty Acids

ABSTRACT The role by which the gut microbiome influences host health (e.g., energy equilibrium and immune system) may be partly mediated by short-chain fatty acids, which are bacterial fermentation products from the dietary fibers. However, little is known about longitudinal changes in gut microbiome metabolites during cohabitation alongside social contact. In common marmosets (Callithrix jacchus), the gut microbiome community is influenced by social contact, as newly paired males and females develop convergent microbial profiles. Here, we monitored the dynamics of short-chain fatty acid concentrations in common marmoset feces from the prepairing (PRE) to postpairing (POST) stages. In males, we observed that the concentrations of acetate, propionate, isobutyrate, and isovalerate significantly increased in the POST stage compared to the PRE stage. However, no significant changes were found in females. We further found that the propionate concentration was significantly positively correlated with the abundance of Phascolarctobacterium in the male feces. Thus, the sex difference in the changes in the concentrations of short-chain fatty acids might be related to sex-biased gut microbiome transmission after pairing. We suggest that the significant changes in the gut microbiomes and some short-chain fatty acids of the common marmoset during cohabitation may contribute to physiological homeostasis during pairing. IMPORTANCE This study addressed a knowledge gap about longitudinal changes in the gut microbiome metabolites during animal pairing. This research in the laboratory common marmoset can control for the confounding factors such as diet and other environmental conditions. Phascolarctobacterium showed the highest contribution to the sex-biased transmission of the female to the male after pairing. Here, we observed the sex difference in the increase in short-chain fatty acid concentration in the feces of newly paired marmosets, which may be caused by the sex-biased gut microbiome transmission after pairing.

scholarly journals Short-Chain Fatty Acids Reduced Renal Calcium Oxalate Stones by Regulating the Expression of Intestinal Oxalate Transporter SLC26A6

mSystems ◽  
2021 ◽  
Author(s):  
Yu Liu ◽  
Xi Jin ◽  
Yucheng Ma ◽  
Zhongyu Jian ◽  
Zhitao Wei ◽  
...  
Keyword(s):  
Fatty Acids ◽  
Fatty Acid ◽  
Gut Microbiota ◽  
Calcium Oxalate ◽  
Renal Stone ◽  
Short Chain Fatty Acid ◽  
Short Chain Fatty Acids ◽  
Chain Fatty Acid ◽  
Short Chain ◽  
Healthy Controls

Some studies found that the relative abundances of short-chain-fatty-acid (SCFA)-producing bacteria were lower in the gut microbiota of renal stone patients than healthy controls. Our previous study demonstrated that SCFAs could reduce the formation of renal calcium oxalate (CaOx) stones, but the mechanism is still unknown.

Short-chain fatty acid, acylation and cardiovascular diseases

2020 ◽  
Vol 134 (6) ◽  
pp. 657-676 ◽  
Author(s):  
Xiao-Feng Chen ◽  
Xiangqi Chen ◽  
Xiaoqiang Tang
Keyword(s):  
Fatty Acids ◽  
Cardiovascular Diseases ◽  
Short Chain Fatty Acid ◽  
Short Chain Fatty Acids ◽  
Chain Fatty Acid ◽  
Short Chain ◽  
Long Chain Fatty Acids ◽  
Metabolic Dysfunction ◽  
Metabolic Pattern ◽  
Chain Fatty Acids

Abstract 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.

Association between the faecal short-chain fatty acid propionate and infant sleep

2020 ◽  
Author(s):  
ALM Heath ◽  
JJ Haszard ◽  
BC Galland ◽  
B Lawley ◽  
NJ Rehrer ◽  
...  
Keyword(s):  
Short Chain Fatty Acid ◽  
Short Chain Fatty Acids ◽  
Chain Fatty Acid ◽  
Short Chain ◽  
Infant Sleep ◽  
Questionnaire Data ◽  
Night Sleep ◽  
Plant Polysaccharides ◽  
Food Components ◽  
Faecal Samples

© 2020, The Author(s), under exclusive licence to Springer Nature Limited. The gut microbiota harvests energy from indigestible plant polysaccharides, forming short-chain fatty acids (SCFAs) that are absorbed from the bowel. SCFAs provide energy—presumably after easily digested food components have been absorbed from the small intestine. Infant night waking is believed by many parents to be due to hunger. Our objective was to determine whether faecal SCFAs are associated with longer uninterrupted sleep in infants. Infants (n = 57) provided faecal samples for determining SCFAs (7 months of age), and questionnaire data for determining infant sleep (7 and 8 months). Linear regression determined associations between SCFAs—faecal acetate, propionate and butyrate—and sleep. For each 1% higher propionate at 7 months of age, the longest night sleep was 6 (95% CI: 1, 10) minutes longer at both 7 and 8 months. A higher proportion of total faecal SCFA as propionate was associated with longer uninterrupted infant sleep.

Short-chain fatty acid propionate improved ventricular electrical remodeling in a rat model with myocardial infarction

2021 ◽  
Author(s):  
Ming-min Zhou ◽  
Di-wen Li ◽  
Ke Xie ◽  
Liao Xu ◽  
Bin Kong ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
Fatty Acids ◽  
Fatty Acid ◽  
Short Chain Fatty Acid ◽  
Short Chain Fatty Acids ◽  
Chain Fatty Acid ◽  
Short Chain ◽  
Electrical Remodeling ◽  
Microbial Fermentation ◽  
Ventricular Electrical Remodeling

Short-chain fatty acids (SCFAs) propionate (C3), a microorganism metabolite produced by gut microbial fermentation, have parasympathetic-activated effects. Cardiac autonomic rebalancing strategy was considered as an important therapeutic approach to myocardial...

scholarly journals Short-Chain Fatty Acid Acetate Stimulates Adipogenesis and Mitochondrial Biogenesis via GPR43 in Brown Adipocytes

Endocrinology ◽  
2016 ◽  
Vol 157 (5) ◽  
pp. 1881-1894 ◽  
Author(s):  
Jiamiao Hu ◽  
Ioannis Kyrou ◽  
Bee K. Tan ◽  
Georgios K. Dimitriadis ◽  
Manjunath Ramanjaneya ◽  
...  
Keyword(s):  
Fatty Acids ◽  
Fatty Acid ◽  
G Protein ◽  
Mitochondrial Biogenesis ◽  
Short Chain Fatty Acid ◽  
Short Chain Fatty Acids ◽  
Chain Fatty Acid ◽  
Short Chain ◽  
Brown Adipocytes ◽  
Mapk Kinase

Abstract Short-chain fatty acids play crucial roles in a range of physiological functions. However, the effects of short-chain fatty acids on brown adipose tissue have not been fully investigated. We examined the role of acetate, a short-chain fatty acid formed by fermentation in the gut, in the regulation of brown adipocyte metabolism. Our results show that acetate up-regulates adipocyte protein 2, peroxisomal proliferator-activated receptor-γ coactivator-1α, and uncoupling protein-1 expression and affects the morphological changes of brown adipocytes during adipogenesis. Moreover, an increase in mitochondrial biogenesis was observed after acetate treatment. Acetate also elicited the activation of ERK and cAMP response element-binding protein, and these responses were sensitive to G(i/o)-type G protein inactivator, Gβγ-subunit inhibitor, phospholipase C inhibitor, and MAPK kinase inhibitor, indicating a role for the G(i/o)βγ/phospholipase C/protein kinase C/MAPK kinase signaling pathway in these responses. These effects of acetate were mimicked by treatment with 4-chloro-α-(1-methylethyl)-N-2-thiazolylbenzeneacetamide, a synthetic G protein-coupled receptor 43 (GPR43) agonist and were impaired in GPR43 knockdown cells. Taken together, our results indicate that acetate may have important physiological roles in brown adipocytes through the activation of GPR43.

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