Effect of betaine on hepatic insulin resistance through FOXO1-induced NLRP3 inflammasome

Kim, Dae Hyun; Kim, Sang Woo; Lee, Bonggi; Lee, Eun Kyeong; Chung, Ki Wung; Moon, Kyoung Mi; An, Hye Jin; Kim, Kyung Mok; Yu, Byung Pal; Chung, Hae Young

doi:10.1016/j.jnutbio.2017.04.014

Cited by 51 publications

(50 citation statements)

References 63 publications

(75 reference statements)

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“…Foxo1 may represent a key link in miR15a regulation of inflammasome actions, as we showed that miR15a directly binds Foxo1. In agreement with this idea is work showing that betaine (a Foxo1 inhibitor) reduced NLRP3 inflammasome formation and IL-1β production (Kim et al, 2017). Future studies will focus on investigating whether Foxo1 is required for miR15a to inhibit NLRP3 inflammasome proteins, and potential mechanisms by which Foxo1 regulates NLRP3 inflammasome proteins in the retina.…”

Section: Discussionmentioning

confidence: 57%

“…Work by Kim et al (2017) showed that Foxo1 stimulated the NLRP3 inflammasome, causing the release of IL-1β in mouse liver and HepG2 cells (Kim et al, 2017). Foxo1 is a transcription factor regulating apoptosis, proliferation, cell stress, and differentiation (Sanchez et al, 2014), and has been implicated in the regulation of IL-1β auto-stimulation in retinal endothelial cells (REC) and diabetic mice retinas (Wu et al, 2017).…”

Section: Introductionmentioning

confidence: 99%

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miR15a regulates NLRP3 inflammasome proteins in the retinal vasculature

Curtiss

Liu

Steinle

2018

Experimental Eye Research

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We have previously published that miR15a can reduce inflammatory cytokines, which could be key to diabetic retinal pathology. In this work, we wanted to investigate whether miR15a altered NLR pyrin domain 3 (NLRP3) proteins. Whole retinal lysates from both miR15a overexpressing mice and endothelial cell specific miR15a/16 knockout mice were used to investigate protein levels of forkhead box protein O1 (Foxo1), NLRP3, cleaved caspase 1 and interleukin-1 beta (IL-1β). Primary human retinal endothelial cells (REC) were cultured in normal and high glucose followed by transfection with a miR15a mimic for protein analyses. MiR15a expression was verified by quantitative PCR, and a luciferase binding assay was used to examine whether miR15a directly bound Foxo1. In mouse retinal lysates, loss of miR15a increased Foxo1, IL-1β, NLRP3, and cleaved caspase 1 levels. REC grown in high glucose transfected with the miR15a mimic had decreased levels of Foxo1 and NLRP3. miR15a directly binds to Foxo1. miR15a regulates NLRP3 actions in the retinal vasculature. Work in mice showed that loss of miR15a increased NLRP3 pathway signaling and Foxo1. miR15a mimics decreased levels of Foxo1 and NLRP3. Taken together, miR15a reduced inflammasome proteins and Foxo1 levels in the retinal vasculature.

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Section: Discussionmentioning

confidence: 57%

Section: Introductionmentioning

confidence: 99%

miR15a regulates NLRP3 inflammasome proteins in the retinal vasculature

Curtiss

Liu

Steinle

2018

Experimental Eye Research

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“…Interestingly, in Southeast Asia, water extracts of Lycium chinensis , which contains a high concentration of betaine, were used as a traditional oriental medicine to treat liver disorders ( 9 ). These findings indicate that the function of betaine, a natural compound, has become a hot topic because of its anti-inflammatory effects on diseases, such as nonalcoholic and alcoholic fatty liver disease (NAFLD and AFLD) and diabetes ( 10 – 12 ). This paper summarizes the role of betaine in physiological functions, anti-inflammatory mechanisms, and human diseases.…”

Section: Introductionmentioning

confidence: 97%

Betaine in Inflammation: Mechanistic Aspects and Applications

et al. 2018

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Betaine is known as trimethylglycine and is widely distributed in animals, plants, and microorganisms. Betaine is known to function physiologically as an important osmoprotectant and methyl group donor. Accumulating evidence has shown that betaine has anti-inflammatory functions in numerous diseases. Mechanistically, betaine ameliorates sulfur amino acid metabolism against oxidative stress, inhibits nuclear factor-κB activity and NLRP3 inflammasome activation, regulates energy metabolism, and mitigates endoplasmic reticulum stress and apoptosis. Consequently, betaine has beneficial actions in several human diseases, such as obesity, diabetes, cancer, and Alzheimer’s disease.

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“…Another potential mechanism involved in the relationship of betaine with diabetes is inflammation. In vitro experiments demonstrated that betaine treatment could significantly inhibit NLRP3 inflammasome-related proteins and the levels of inflammatory cytokines including IL-1β [39]. Therefore, high betaine levels may play a protective role in diabetes related metabolic disorders.…”

Section: Discussionmentioning

confidence: 99%

Low serum betaine levels as a potential biomarker for type 2 diabetes mellitus in patients with coronary artery disease

Guo

Qiu

Zhu

et al. 2020

Preprint

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Background Dietary betaine intake was reported to associate with improved metabolic profile in type 2 diabetes (T2D). However, the role of circulating betaine in coronary artery disease (CAD) patients with T2D is still unknown. This study aimed to investigate the potential role of serum betaine as a potential biomarker for T2D risk in CAD patients. Methods Total 307 subjects were enrolled with 165 CAD patients (57 with T2D and 108 without) and 142 age and sex matched controls (CON). Fasting serum betaine were detected using liquid chromatography tandem mass spectrometry. Results Serum betaine were lower in simple CAD patients compared with healthy controls, and were further decreased in CAD patients with T2D. Betaine was inversely associated with fasting glucose. Subjects in the highest betaine tertile group had lower triglycerides, total cholesterol and low-density lipoprotein as well was lower percentage of CAD and T2D. Increased betaine in CAD was independently associated with low risk of T2D. Furthermore, betaine was a potential diagnostic marker in distinguishing simple CAD from CAD with T2D. Conclusion Low levels of betaine are associated with increased risk of CAD and T2D in CAD, and could be a biomarker for predicting T2D in CAD.

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Effect of betaine on hepatic insulin resistance through FOXO1-induced NLRP3 inflammasome

Cited by 51 publications

References 63 publications

miR15a regulates NLRP3 inflammasome proteins in the retinal vasculature

miR15a regulates NLRP3 inflammasome proteins in the retinal vasculature

Betaine in Inflammation: Mechanistic Aspects and Applications

Low serum betaine levels as a potential biomarker for type 2 diabetes mellitus in patients with coronary artery disease

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