Short-chain fatty acid mitigates adenine-induced chronic kidney disease via FFA2 and FFA3 pathways

Mikami, Daisuke; Kobayashi, Mamiko; Uwada, Junsuke; Yazawa, Takashi; Kamiyama, Kazuko; Nishimori, Kazuhisa; Nishikawa, Yudai; Nishikawa, Satoru; Yokoi, Seiji; Kimura, Hideki; Kimura, Ikuo; Taniguchi, Tadatsugu; Iwano, Masayuki

doi:10.1016/j.bbalip.2020.158666

Cited by 19 publications

(13 citation statements)

References 25 publications

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“…MPO is an enzyme expressed in neutrophils, and has been used as an indicator for neutrophil infiltration. 17 Butyrate treatments (300 mg/kg) before renal I/R remarkably suppressed the MPO activities in kidney tissue. In this study, we demonstrated the suppressive effects of butyrate against MPO activities in renal I/R, indicating butyrate attenuated the renal damages caused by inflammation through the inhibition of oxidative stress.…”

Section: Discussionmentioning

confidence: 90%

Quantitative Increase in Short-Chain Fatty Acids, Especially Butyrate Protects Kidney from Ischemia/Reperfusion Injury

Sun

Zhou

Chen

et al. 2022

Journal of Investigative Medicine

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Short-chain fatty acids (SCFAs), the end products of fermentation carried out by the intestinal microbiota, were demonstrated to produce anti-oxidant and anti-inflammatory effects. Butyrate, part of the SCFAs, also shows the same effect. Renal ischemia/reperfusion (I/R) injury commonly occurs in renal transplantation and is often accompanied by oxidative stresses and inflammatory responses. In this study, we explore butyrate effect on renal I/R injury and SCFAs changes in renal transplant. Male Sprague-Dawley rats were pretreated with butyrate as research, and underwent the surgery of renal ischemia for 45 min followed by reperfusion. 90 rats were randomly divided into 3 groups (n=30 each group): (1) sham-operated group; (2) butyrate-treated group; (3) control group. The samples of blood and renal were collected immediately for further studies. Thirty-two patients were enrolled to investigate the levels of SCFAs after the renal transplantation. Rats model showed that butyrate treatments significantly enhanced the function and structure of kidney, as evidenced by the lower serum creatinine levels and less pathological damages of renal tissue. With the recovery of renal function after renal transplantation, SCFAs increased, which were negatively correlated with creatinine. Butyrate expressed like SCFAs. In this study, we demonstrated that butyrate increased with the recovery of renal function after renal transplantation. Most importantly, butyrate treatments alleviated the renal damages caused by I/R via the upregulation of intracellular oxidant stress and inflammations.

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Section: Discussionmentioning

confidence: 90%

Quantitative Increase in Short-Chain Fatty Acids, Especially Butyrate Protects Kidney from Ischemia/Reperfusion Injury

Sun

Zhou

Chen

et al. 2022

Journal of Investigative Medicine

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“…Step (4). In a pre-dried round-bottom flask under argon, 2-(4-(trifluoromethyl)phenyl)acetaldehyde (5.02 g), (S)-(À )-2methyl-2-propanesulfinamide (3.25 g, 26.8 mmol), and pyridinium (5). To a pre-dried microwave vial were added 4 (4.45 g, 15.3 mmol), dimethyl malonate (2.90 mL, 30.6 mmol) and NaI (2.29 g, 15.3 mmol).…”

Section: (S)-3-(2-(3-chlorophenyl)acetamido)-4-(4-(trifluoromethyl)phenyl) Butanoic Acid (1)mentioning

confidence: 99%

“…The animals were randomly assigned to the treatment groups before the pharmacokinetic study; all animals were fasted for 4 h before dosing. Nine time points (5,15,30,60,120,240,360,480, and 1440 min) were set for this pharmacokinetic study. Each of the time point treatment group included 4 animals.…”

Section: In Vivo Pharmacokineticsmentioning

confidence: 99%

“…The free fatty acid receptor 2 (FFA2) and the closely related FFA3 are G protein-coupled receptors that sense short-chain fatty acids (SCFAs) such as acetate, propionate and butyrate, [1] and that have been implicated in mediation of the physiological effects of SCFA-producing gut microbiota. [2] FFA2 is relatively broadly expressed in immune cells, intestine, adipose tissue and pancreas, [3] and has been suggested as a target for treatment of metabolic disorders, such as type 2 diabetes [4] and chronic kidney disease, [5] inflammatory disorders, including inflammatory bowel disease [6] and allergic asthma, [7] as well as infectious diseases. [8] Antagonists were suggested for treatment of type 2 diabetes based on results from FFA2 and FFA3 knockout mice.…”

Section: Introductionmentioning

confidence: 99%

“…6.96 (s, 1H),6.93 (d, J = 7.5 Hz, 1H),6.00 (d, J = 8 5. Hz, 1H), 4.52-4.38 (m, 1H), 3.62 (s, 3H), 3.44 (s, 2H), 2.90 (dd, J = 13.7, 7.3 Hz, 1H), 2.82 (dd, J = 13.7, 7.0 Hz, 1H), 2.53-2.40 (m, 2H), 2.32 (s, 3H); 13 C NMR (101 MHz, CDCl 3 ) δ 171.8, 170.7, 141.6 (app s), 138.8, 134.6, 130.2, 129.7 (2 C), 129.6, 129.3, 129.0, 128.6, 128.2, 126.4, 125.5 (q, J = 3.7 Hz, 2 C), 124.3 (q, J = 271.9 Hz), 51.8, 47.3, 44.0, 39.5, 37.3, 21.4; HRMS (ESI) calcd for C 21 H 22 F 3 NNaO 3 (M + Na + ) 416.1444, found 416.1442.…”

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confidence: 99%

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Structure‐Activity Relationship Explorations and Discovery of a Potent Antagonist for the Free Fatty Acid Receptor 2

et al. 2021

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Free fatty acid receptor 2 (FFA2) is a sensor for short-chain fatty acids that has been identified as an interesting potential drug target for treatment of metabolic and inflammatory diseases. Although several ligand series are known for the receptor, there is still a need for improved compounds. One of the most potent and frequently used antagonists is the amide-substituted phenylbutanoic acid known as CATPB (1). We here report the structure-activity relationship exploration of this compound, leading to the identification of homologues with increased potency. The preferred compound 37 (TUG-1958) was found, besides improved potency, to have high solubility and favorable pharmacokinetic properties.

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The modulation effects of plant‐derived bioactive ingredients on chronic kidney disease: Focus on the gut–kidney axis

et al. 2023

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Chronic kidney disease (CKD) results mainly from diabetes, hypertension, and glomerulonephritis, which can develop into end-stage renal disease and CKD-related complications, thereby causing high morbidity and mortality. This progression is correlated with pathogenic alterations in the gut microbiota that generate uremic toxins, mainly including indoxyl sulfate, p-cresol sulfate, and trimethylamine-N-oxide. The uremic toxins directly or indirectly induce CKD through oxidative stress, inflammatory response, and subsequently renal fibrosis. However, ongoing developments in CKD therapy still lack nutritional guidelines and new pharmacotherapies with significant effects. In this review, we discuss the modulatory effects of plant-derived bioactive ingredients, such as dietary fiber (oligosaccharides and polysaccharides), polyphenols (e.g., curcumin, anthocyanins, catechins, and resveratrol), and peptides, on gut microbiota and CKD particularly from the view of the gut-kidney axis. We believe that a comprehensive understanding of the underlying mechanisms of CKD is necessary to develop new targeted therapy strategies that will benefit the prevention and treatment of CKD.

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Short-chain fatty acid mitigates adenine-induced chronic kidney disease via FFA2 and FFA3 pathways

Cited by 19 publications

References 25 publications

Quantitative Increase in Short-Chain Fatty Acids, Especially Butyrate Protects Kidney from Ischemia/Reperfusion Injury

Quantitative Increase in Short-Chain Fatty Acids, Especially Butyrate Protects Kidney from Ischemia/Reperfusion Injury

Structure‐Activity Relationship Explorations and Discovery of a Potent Antagonist for the Free Fatty Acid Receptor 2

The modulation effects of plant‐derived bioactive ingredients on chronic kidney disease: Focus on the gut–kidney axis

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