Sodium acetate-mediated inhibition of histone deacetylase alleviates hepatic lipid dysregulation and its accompanied injury in streptozotocin-nicotinamide-induced diabetic rats

Olaniyi, Kehinde S.; Amusa, Oluwatobi A.

doi:10.1016/j.biopha.2020.110226

Cited by 25 publications

(14 citation statements)

References 41 publications

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“…It is widely known that SCFAs inhibit HDAC activity in many cell types, and previous studies have shown that butyrate, and to a lesser extent, propionate acts as an HDAC inhibitor, exerting effects on the inflammatory process by downregulating the expression of pro-inflammatory genes (29)(30)(31). In addition, acetate can also act as an HDAC inhibitor (32,33). In our study, we demonstrated that SCFAs induced HIF-1a expression in HKMs via the inhibition of HDACs.…”

Section: Discussionsupporting

confidence: 62%

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: Discussionsupporting

confidence: 62%

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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“…Intriguingly, administration of acetate, an inhibitor of HDAC significantly increased plasma, hypothalamic and adipose PPAR-γ concentration with corresponding improvement in insulin sensitivity and glucose regulation as well as hypothalamic and adipose lipid metabolism, lipid peroxidation, G6PD/GSH-dependent antioxidant capacity, NO, inflammatory mediators and normalized leptin concentration, visceral adiposity and body weight in OBS + ACT group compared to untreated obese group. A number of studies have documented acetate as HDAC inhibitor 39 , 68 , 69 , and acetate has been earlier shown to improve insulin sensitivity and exert anti-inflammatory effects against neuroinflammation, hypertension and hyperandrogenism among others 38 , 40 , 41 , 70 . Similarly, the present results are also in line with the observation of Lee et al, who revealed that the inhibition of HDAC by MPT0E014 attenuated cardiomyopathy by upregulation of PPAR-γ 71 .…”

Section: Discussionmentioning

confidence: 99%

“…It improves intestinal mucosa integrity/immunity, enhance insulin sensitivity and exert anti-inflammatory effects. Earlier studies demonstrated that oral supplementation with acetate exerts recovery from hepatic lipotoxicity 38 , 39 , neuroinflammation 40 , and hypertension 41 . However, the effects of acetate on disrupted brain-adipose metabolic link and/or brain-adipose inflammatory events underlying obesity was not known.…”

Section: Introductionmentioning

confidence: 99%

Acetate rescues defective brain-adipose metabolic network in obese Wistar rats by modulation of peroxisome proliferator-activated receptor-γ

Olaniyi

Owolabi

Atuma

et al. 2021

Sci Rep

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We investigated the hypothesis that acetate ameliorates brain-adipose metabolic dysfunction (BAMED) in high fat diet (HFD)-induced obesity, possibly by modulation of peroxisome proliferator-activated receptor-γ (PPAR-γ). Ten-week-old male Wistar rats were randomly assigned into four groups (n = 6/group): Control, acetate and obese with or without acetate groups received vehicle (distilled water; po), acetate (200 mg/kg, po) and 40% HFD with or without acetate respectively. The treatments lasted for 12 weeks. Obese animals showed increase in body weight, visceral fat mass, insulin and triglyceride-glucose index and a reduction in insulin sensitivity. In addition, obese animals also showed increase in plasma/hypothalamic and adipose pyruvate dehydrogenase kinase-4, lactate-pyruvate ratio, malondialdehyde, γ-glutamyl transferase, and a decrease in glucose-6-phosphate dehydrogenase, glutathione, nitric oxide and PPAR-γ. HFD also elevated plasma/hypothalamic lipid and decreased adipose lipid profile, increased hypothalamic and adipose tumor necrosis factor-α, interleukin-6 and histone deacetylase (HDAC), and elevated plasma/adipose leptin. These alterations were reversed by concomitant administration of acetate. The present results demonstrate that obesity is characterized by BAMED, which is accompanied by altered HDAC/PPAR-γ. The results in addition suggest that acetate, an HDAC inhibitor rescues BAMED with consequent normalization of body weight and visceral fat mass by modulation of PPAR-γ and suppression of oxidative stress.

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“…This may be because of the high mitochondrial and lipogenic demand for two-carbon acetyl units from exogenous acetate in adipocytes, leaving it to contribute to histone acetylation only sparingly [ 50 ]. However, acetate can inhibit HDACs in the liver, leading to amelioration of hepatic lipid dysregulation and enhancement of insulin sensitivity in diabetic rats [ 51 ] Moreover, acetate released from histone deacetylation can be “recaptured” to supply the acetyl units for HATs [ 50 ], indicating a complex role of acetate in histone acetylation.…”

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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Sodium acetate-mediated inhibition of histone deacetylase alleviates hepatic lipid dysregulation and its accompanied injury in streptozotocin-nicotinamide-induced diabetic rats

Cited by 25 publications

References 41 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

Acetate rescues defective brain-adipose metabolic network in obese Wistar rats by modulation of peroxisome proliferator-activated receptor-γ

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

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