Short-Chain Fatty Acids and Their Association with Signalling Pathways in Inflammation, Glucose and Lipid Metabolism

He, Jin; Zhang, Peiwen; Shen, Linyuan; Niu, Lili; Tan, Yimin; Chen, Lei; Zhao, Ye; Bai, Lin; Hao, Xiaoxia; Li, Xuewei; Zhang, Shunhua; Zhu, Li

doi:10.3390/ijms21176356

Cited by 547 publications

(398 citation statements)

References 138 publications

(155 reference statements)

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“…To date, the mechanism by which SCFAs inhibit HDACs is still unclear. It appears that SCFAs may directly act on HDACs via different transporters on the cells, or indirectly through GPCR activation ( 34 ). Our results, however, have indicated that SCFAs enter into target cells and act inside these cells, since we demonstrated that GPCRs were not involved in SCFA-induced responses ( Figure 5E ).…”

Section: Discussionmentioning

confidence: 99%

Short-Chain Fatty Acids Promote Intracellular Bactericidal Activity in Head Kidney Macrophages From Turbot (Scophthalmus maximus L.) via Hypoxia Inducible Factor-1α

Zhang

Liu

et al. 2020

Front. Immunol.

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Short-chain fatty acids (SCFAs) are mainly produced by microbiota through the fermentation of carbohydrates in the intestine. Acetate, propionate, and butyrate are the most abundant SCFA metabolites and have been shown to be important in the maintenance of host health. In this study, head kidney macrophages (HKMs) were isolated and cultured from turbots. We found that the antibacterial activity of HKMs was increased after these cells were incubated with sodium butyrate, sodium propionate or sodium acetate. Interestingly, our results showed that all three SCFAs enhanced the expression of hypoxia inducible factor-1 α (HIF-1α) in HKMs, and further study confirmed that butyrate augmented the oxygen consumption of these cells. Moreover, HIF-1α inhibition diminished the butyrate-promoted intracellular bacterial killing activity of macrophages, and SCFAs also raised the gene expression and activity of lysozymes in HKMs via HIF-1α signaling. In addition, our results suggested that butyrate induced HIF-1α expression and the bactericidal activity of HKMs through histone deacetylase inhibition, while G protein-coupled receptors did not contribute to this effect. Finally, we demonstrated that butyrate induced a similar response in the murine macrophage cell line RAW264.7. In conclusion, our results demonstrated that SCFAs promoted HIF-1α expression via histone deacetylase inhibition, leading to the enhanced production of antibacterial effectors and increased bacterial killing of macrophages.

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Section: Discussionmentioning

confidence: 99%

Short-Chain Fatty Acids Promote Intracellular Bactericidal Activity in Head Kidney Macrophages From Turbot (Scophthalmus maximus L.) via Hypoxia Inducible Factor-1α

Zhang

Liu

et al. 2020

Front. Immunol.

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“…Due to a lack of the enzymes essential for digestion of dietary fiber in the human gut, SCFAs are the primary metabolites from the fermentation of incompletely hydrolyzed dietary foods by specific gut microbiota in the colon through various pathways ( Table 1 ) [ 4 ]. The total concentration of SCFAs in the gut is 0.5–0.6 mol per day [ 24 ] depending on the diet, bacterial composition of the gut, and intestinal transit time [ 25 ]. Acetate (C2), propionate (C3), and butyrate (C4) are the most abundant SCFAs found in the gut (≥95%) with a molar ratio of roughly 3 : 1 : 1, respectively [ 3 ].…”

Section: Overview Of Scfasmentioning

confidence: 99%

“…The opposing enzymes, histone acetyltransferases (HATs), transfer the acetyl group of acetyl-CoA to histones, dissociate DNA from histone octamers, relax the nucleosome structure, make transcription factors bind to DNA-binding sites, and activate gene transcription. HATs and HDACs maintain acetylation of histone and nonhistone proteins in dynamic equilibrium to regulate physiological functions, such as inflammation, pancreas development, glucose metabolism, and insulin signaling [ 24 , 42 ]. However, overexpression and aberrant recruitment of HDACs are associated with T2DM pathogenesis [ 43 ].…”

Section: Overview Of Scfasmentioning

confidence: 99%

Modulation of Short-Chain Fatty Acids as Potential Therapy Method for Type 2 Diabetes Mellitus

Tang

2021

Canadian Journal of Infectious Diseases and Medical Microbiolog

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In recent years, the relationship between intestinal microbiota (IM) and the pathogenesis of type 2 diabetes mellitus (T2DM) has attracted much attention. The beneficial effects of IM on the metabolic phenotype of the host are often considered to be mediated by short-chain fatty acids (SCFAs), mainly acetate, butyrate, and propionate, the small-molecule metabolites derived from microbial fermentation of indigestible carbohydrates. SCFAs not only have an essential role in intestinal health but might also enter the systemic circulation as signaling molecules affecting the host’s metabolism. In this review, we summarize the effects of SCFAs on glucose homeostasis and energy homeostasis and the mechanism through which SCFAs regulate the function of metabolically active organs (brain, liver, adipose tissue, skeletal muscle, and pancreas) and discuss the potential role of modulation of SCFAs as a therapeutic method for T2DM.

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“…The participation of SCFAs in two major signaling pathways involved in metabolic inflammation, glucose, and lipid metabolism is well known [ 53 ]. Numerous studies have shown correlations between SCFAs, BMI, body fat distribution, and fat to lean mass ratio in children [ 54 ].…”

Section: Discussionmentioning

confidence: 99%

In Vitro Modulatory Effect of Stevioside, as a Partial Sugar Replacer in Sweeteners, on Human Child Microbiota

2021

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The effect of stevioside on human health is still insufficiently highlighted by recent research. The total or partial replacement of sugar with sweeteners influences the general state of health, especially the human microbiota’s response as a determining factor in the onset of type 2 diabetes. The present study aimed to present the long-term (one-year) in vitro effect that regular stevioside consumption had on children’s pattern microbiota. A metabolomic response was established by determining the synthesis of organic acids and a correlation with antioxidant status. An increase in the number of bacterial strains and the variation of amount of butyrate and propionate to the detriment of lactic acid was observed. The effect was evidenced by the progressive pH increasing, the reduction of acetic acid, and the proliferation of Escherichia coli strains during the simulations. Synthesis of the main short-chain fatty acids (SCFAs) was interpreted as a response (adaptation) of the microbiota to the stevioside, without a corresponding increase in antioxidant status. This study demonstrated the modulatory role of stevioside on the human microbiota and on the fermentation processes that determine the essential SCFA synthesis in maintaining homeostasis. The protection of the microbiota against oxidative stress was also an essential aspect of reducing microbial diversity.

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Short-Chain Fatty Acids and Their Association with Signalling Pathways in Inflammation, Glucose and Lipid Metabolism

Cited by 547 publications

References 138 publications

Short-Chain Fatty Acids Promote Intracellular Bactericidal Activity in Head Kidney Macrophages From Turbot (Scophthalmus maximus L.) via Hypoxia Inducible Factor-1α

Short-Chain Fatty Acids Promote Intracellular Bactericidal Activity in Head Kidney Macrophages From Turbot (Scophthalmus maximus L.) via Hypoxia Inducible Factor-1α

Modulation of Short-Chain Fatty Acids as Potential Therapy Method for Type 2 Diabetes Mellitus

In Vitro Modulatory Effect of Stevioside, as a Partial Sugar Replacer in Sweeteners, on Human Child Microbiota

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