Sphingomyelin maintains the cutaneous barrier via regulation of the STAT3 pathway

Komuro, Mariko; Nagane, Masaki; Fukuyama, Tomoki; Luo, Xiaolin; Hiraki, Shinobu; Miyanabe, Masakatsu; Ishikawa, Miyuki; Niwa, Chiaki; Murakami, Hironobu; Okamoto, Mariko; Yamashita, Tadashi

doi:10.1096/fj.202100721rr

Cited by 10 publications

(7 citation statements)

References 67 publications

(115 reference statements)

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“…RT‐qPCR was performed as previously described with modifications 21 . Total RNA dissolved from the colon of mice was purified using the Tissue Total RNA Mini Kit (catalog no.…”

Section: Methodsmentioning

confidence: 99%

“…Western blot was performed as described in a previous study. 21 Cells were lysed using modified RIPA Buffer and subjected to sonication with BIORUPTOR® II TYPE6 (Cat. No.…”

Section: Western Blotmentioning

confidence: 99%

“…RT-qPCR was performed as previously described with modifications. 21 Total RNA dissolved from the colon of mice was purified using the Tissue Total RNA Mini Kit (catalog no. FATRK 001; Favorgen Biotech Corporation, Ping-Tung, Taiwan) according to the manufacturer's instructions.…”

Section: Reverse Transcription-quantitative Polymerase Chain Reaction...mentioning

confidence: 99%

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The novel sustained 3‐hydroxybutyrate donor poly‐D ‐3‐hydroxybutyric acid prevents inflammatory bowel disease through upregulation of regulatory T‐cells

et al. 2022

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Inflammatory bowel disease (IBD) is a chronic persistent intestinal disorder, with ulcerative colitis and Crohn's disease being the most common. However, the physio-pathological development of IBD is still unknown. Therefore, research on the etiology and treatment of IBD has been conducted using a variety of approaches. Short-chain fatty acids such as 3-hydroxybutyrate (3-HB) are known to have various physiological activities. In particular, the production of 3-HB by the intestinal microflora is associated with the suppression of various inflammatory diseases. In this study, we investigated whether poly-D-3-hydroxybutyric acid (PHB), a polyester of 3-HB, is degraded by intestinal microbiota and works as a slow-release agent of 3-HB. Further, we examined whether PHB suppresses the pathogenesis of IBD models. As long as a PHB diet increased 3-HB concentrations in the feces and blood, PHB suppressed weight loss and histological inflammation in a dextran sulfate sodium-induced IBD model. Furthermore, PHB increased the accumulation of regulatory T cells in the rectum without affecting T cells in the spleen. These results indicate that PHB has potential applications in treating diseases related to the intestinal microbiota as a sustained 3-HB donor. We show for the first time that biodegradable polyester exhibits intestinal bacteria-mediated bioactivity toward IBD. The use of bioplastics, which are essential materials for How to cite this article: Suzuki R, Mishima M, Nagane M, et al. The novel sustained 3-hydroxybutyrate donor poly-D-3-hydroxybutyric acid prevents inflammatory bowel disease through upregulation of regulatory T-cells.

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“…RT‐qPCR was performed as previously described with modifications 21 . Total RNA dissolved from the colon of mice was purified using the Tissue Total RNA Mini Kit (catalog no.…”

Section: Methodsmentioning

confidence: 99%

“…Western blot was performed as described in a previous study. 21 Cells were lysed using modified RIPA Buffer and subjected to sonication with BIORUPTOR® II TYPE6 (Cat. No.…”

Section: Western Blotmentioning

confidence: 99%

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The novel sustained 3‐hydroxybutyrate donor poly‐D ‐3‐hydroxybutyric acid prevents inflammatory bowel disease through upregulation of regulatory T‐cells

et al. 2022

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“…Quantitative reverse transcription PCR (RT-qPCR) analysis was performed as previously described, with modifications. 29 First, liver tissue was lysed using RNAiso plus (Cat. No.…”

Section: Pcr Analysismentioning

confidence: 99%

Prebiotic effect of poly‐D‐3‐hydroxybutyrate prevents dyslipidemia in obese mice

Mishima,

Takeda,

Nagane

et al. 2023

The FASEB Journal

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Obesity is a global health problem caused by genetic, environmental, and psychological factors and is associated with various health disorders. As such, there is a growing focus on the prevention of obesity and related diseases. The gut microbiota plays a crucial role in these diseases and has become a therapeutic target. Prebiotics, such as poly‐d‐3‐hydroxybutyric acid (PHB), have gained attention for their potential to alter the gut microbiota, promote beneficial bacterial growth, and alleviate obesity. In this study, we examined the prebiotic effects of PHB in obese mice. We found that, in C57BL/6N mice, PHB reduced blood lipid levels. Analysis of the intestinal microflora also revealed an increase in short‐chain fatty acid‐producing bacteria. When PHB was administered to obese mice, subcutaneous fat and dyslipidemia were reduced, and the number of beneficial bacteria in the intestinal microflora increased. Furthermore, fatty degradation and oxidative stress were suppressed in the liver. PHB regulates gut bacterial changes related to obesity and effectively inhibits dyslipidemia, suggesting that it could be a prebiotic agent for curing various obesity‐related diseases. In summary, PHB increases the beneficial gut microbiota, leading to an alleviation of obesity‐associated dyslipidemia.

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“…Sphingomyelin, a sphingolipid providing ceramides via a hydrolysis pathway, can also contribute to the maintenance of the skin barrier via phosphorylation of the signal transducer and activator of transcription 3 (STAT3) [29]. Furthermore, mutations in the very long chain fatty acid elongase (ELOVL)4, providing acyl chains for stratum corneum ceramides, are linked to barrier problems in ichthyosis [30 ▪ ], while increased levels of glucosylcholesterol in children with atopic dermatitis can also contribute to a compromised barrier [31].…”

Section: Lipids Have Different Roles Throughout the Skinmentioning

confidence: 99%

Current insights into skin lipids and their roles in cutaneous health and disease

Nicolaou

Kendall²

2022

Current Opinion in Clinical Nutrition &Amp; Metabolic Care

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Purpose of reviewThe unique and complex array of cutaneous lipids include essential components of the skin structure and signalling molecules mediating homeostasis and inflammation. Understanding skin lipid biology and metabolism can support our comprehension of health and disease, including systemic conditions with cutaneous involvement.Recent findingsLipids found on the skin surface, produced by both the host and resident microbes, maintain and regulate the skin microbiome and the epidermal barrier, whilst altered contributions from either source can be detrimental to skin health. The unique lipid composition of the epidermal barrier is essential for its function, and recent studies have expanded our understanding of epidermal ceramide production. This has been supported by improved models available for skin research, including organotypic skin models enabling in-vitro production of complex acylceramides for the first time, and model systems facilitating in-silico exploration of the lipid profile changes observed in clinical samples. Studies have revealed further involvement of lipid mediators such as eicosanoids in cutaneous inflammation, as well as immune regulation in both healthy and diseased skin.SummarySkin lipids offer exciting opportunities as therapeutic targets for many conditions, whether through topical interventions or nutritional supplementation.

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Sphingomyelin maintains the cutaneous barrier via regulation of the STAT3 pathway

Cited by 10 publications

References 67 publications

The novel sustained 3‐hydroxybutyrate donor poly‐D ‐3‐hydroxybutyric acid prevents inflammatory bowel disease through upregulation of regulatory T‐cells

The novel sustained 3‐hydroxybutyrate donor poly‐D ‐3‐hydroxybutyric acid prevents inflammatory bowel disease through upregulation of regulatory T‐cells

Prebiotic effect of poly‐D‐3‐hydroxybutyrate prevents dyslipidemia in obese mice

Current insights into skin lipids and their roles in cutaneous health and disease

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