Glycaemia and body weight are regulated by sodium-glucose cotransporter 1 (SGLT1) expression via O-GlcNAcylation in the intestine

Nishimura, K.; Fujita, Yukihiro; Ida, Shogo; Yanagimachi, Tsuyoshi; Ohashi, Nobuhide; Nishi, Kiyoto; Nishida, Atsushi; Iwasaki, Yoshinobu; Morino, Katsutaro; Ugi, Satoshi; Nishi, Eiichiro; Andoh, Akira; Maegawa, Hiroshi

doi:10.1016/j.molmet.2022.101458

Cited by 10 publications

(11 citation statements)

References 39 publications

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“…Glucose is one of the most important energy sources in animals, and GluT1 is a uniporter protein that is located on the cell membrane or cell surface and helps transport glucose into mammalian cells ( 49 ). The sustained expression of GluT1 protein enables efficient glucose transport and glucose utilization, and then glucose is absorbed by the active sugar transporter SglT1 at the brush border of intestinal epithelial cells ( 50 ). In recent years, oligopeptide transporter 1 ( PepT1 ) was found to play a key role in intestinal homeostasis in metabolite profiling and tissue physiology ( 51 ).…”

Section: Discussionmentioning

confidence: 99%

Eugenol alleviates transmissible gastroenteritis virus-induced intestinal epithelial injury by regulating NF-κB signaling pathway

Wang

Chen²,

Yu³

et al. 2022

Front. Immunol.

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Increasing evidence supports the ability of eugenol to maintain intestinal barrier integrity and anti-inflammatory in vitro and in vivo; however, whether eugenol alleviates virus-mediated intestinal barrier damage and inflammation remains a mystery. Transmissible gastroenteritis virus (TGEV), a coronavirus, is one of the main causative agents of diarrhea in piglets and significantly impacts the global swine industry. Here, we found that eugenol could alleviate TGEV-induced intestinal functional impairment and inflammatory responses in piglets. Our results indicated that eugenol improved feed efficiency in TGEV-infected piglets. Eugenol not only increased serum immunoglobulin concentration (IgG) but also significantly decreased serum inflammatory cytokine concentration (TNF-α) in TGEV-infected piglets. In addition, eugenol also significantly decreased the expression of NF-κB mRNA and the phosphorylation level of NF-κB P65 protein in the jejunum mucosa of TGEV-infected piglets. Eugenol increased villus height and the ratio of villus height to crypt depth in the jejunum and ileum, and decreased serum D-lactic acid levels. Importantly, eugenol increased tight junction protein (ZO-1) and mRNA expression levels of nutrient transporter-related genes (GluT-2 and CaT-1) in the jejunum mucosa of TGEV-infected piglets. Meanwhile, compared with TGEV-infected IPEC-J2 cells, treatment with eugenol reduced the cell cytopathic effect, attenuated the inflammatory response. Interestingly, eugenol did not increase the expression of ZO-1 and Occludin in IPEC-J2 cells. However, western blot and immunofluorescence results showed that eugenol restored TGEV-induced down-regulation of ZO-1 and Occludin, while BAY11-7082 (The NF-κB specific inhibitor) enhanced the regulatory ability of eugenol. Our findings demonstrated that eugenol attenuated TGEV-induced intestinal injury by increasing the expression of ZO-1 and Occludin, which may be related to the inhibition of NF-κB signaling pathway. Eugenol may offer some therapeutic opportunities for coronavirus-related diseases.

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Section: Discussionmentioning

confidence: 99%

Eugenol alleviates transmissible gastroenteritis virus-induced intestinal epithelial injury by regulating NF-κB signaling pathway

Wang

Chen²,

Yu³

et al. 2022

Front. Immunol.

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“…Thus, the double-edged sword potential of O-GlcNAcylation is clearly revealed by these studies in the gut, with both deleterious [87] and beneficial [88] effects of OGT deletion in the same tissue. A very recent study [89] by Nishimura et al further revealed the complexity of O-GlcNAcylation involvement in the control of intestinal homeostasis. These authors showed that OGT-KO in intestinal epithelial cells resulted in decreased body weight and glycaemia in the fed state, decreased glycaemia excursion during an oral glucose tolerance test, decreased intestinal sugar absorption from the small intestine, associated with reduced expression of the glucose transporter SGLT1.…”

Section: Ogt Knock-out In the Intestinementioning

confidence: 99%

“…In contrast to the study of Zhao et al [87] which showed marked inflammation in the lower small intestine and in the colon in OGT-KO mice, Nishimura et al found no inflammation in the upper small intestine. These authors suggested that discrepancies between these studies might arise from their focus on different part of the intestine and/or from difference in the gut bacterial flora, which can markedly differ between laboratories [89].…”

Section: Ogt Knock-out In the Intestinementioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

“…found no inflammation in the upper small intestine. These authors suggested that discrepancies between these studies might arise from their focus on different part of the intestine and/or from difference in the gut bacterial flora, which can markedly differ between laboratories [ 89 ].…”

Section: Introductionmentioning

confidence: 99%

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Protein O-GlcNAcylation and the regulation of energy homeostasis: lessons from knock-out mouse models

et al. 2022

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O-GlcNAcylation corresponds to the addition of N-Acetylglucosamine (GlcNAc) on serine or threonine residues of cytosolic, nuclear and mitochondrial proteins. This reversible modification is catalysed by a unique couple of enzymes, O-GlcNAc transferase (OGT) and O-GlcNAcase (OGA). OGT uses UDP-GlcNAc produced in the hexosamine biosynthesis pathway, to modify proteins. UDP-GlcNAc is at the cross-roads of several cellular metabolisms, including glucose, amino acids and fatty acids. Therefore, OGT is considered as a metabolic sensor that post-translationally modifies proteins according to nutrient availability. O-GlcNAcylation can modulate protein–protein interactions and regulate protein enzymatic activities, stability or subcellular localization. In addition, it can compete with phosphorylation on the same serine or threonine residues, or regulate positively or negatively the phosphorylation of adjacent residues. As such, O-GlcNAcylation is a major actor in the regulation of cell signaling and has been implicated in numerous physiological and pathological processes. A large body of evidence have indicated that increased O-GlcNAcylation participates in the deleterious effects of glucose (glucotoxicity) in metabolic diseases. However, recent studies using mice models with OGT or OGA knock-out in different tissues have shown that O-GlcNAcylation protects against various cellular stresses, and indicate that both increase and decrease in O-GlcNAcylation have deleterious effects on the regulation of energy homeostasis.

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Lead exposure aggravates glucose metabolism disorders through gut microbiota dysbiosis and intestinal barrier damage in high‐fat diet‐fed mice

Wang,

Gao,

Huo

et al. 2023

J Sci Food Agric

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BACKGROUNDLead (Pb) is an ancient toxic metal and is still a major public health issue. Our previous study found that Pb exposure promotes metabolic disorders in obese mice, but the molecular mechanisms remain unclear. The present study explored the effects of Pb exposure on glucose homeostasis in mice fed a normal diet (ND) and high‐fat diet (HFD) from the perspective of gut microbiota.RESULTSPb exposure had little effect on glucose metabolism in ND mice, but exacerbated hyperglycemia and insulin resistance, and impaired glucose tolerance in HFD mice. Pb exposure impaired intestinal tight junctions and mucin expression in HFD mice, increasing intestinal permeability and inflammation. Moreover, Pb exposure altered the composition and structure of the gut microbiota and decreased short‐chain fatty acids (SCFAs) levels in HFD mice. Correlation analysis revealed that the gut microbiota and SCFAs were significantly correlated with the gut barrier and glucose homeostasis. Furthermore, the fecal microbiota transplantation from Pb‐exposed HFD mice resulted in glucose homeostasis imbalance, intestinal mucosal structural damage and inflammation in recipient mice. However, Pb did not exacerbate the metabolic toxicity in HFD mice under depleted gut microbiota.CONCLUSIONThe findings of the present study suggest that Pb induces impairment of glucose metabolism in HFD mice by perturbing the gut microbiota. Our study offers new perspectives on the mechanisms of metabolic toxicity of heavy metals and demonstrates that the gut microbiota may be a target of action for heavy metal exposure. © 2023 Society of Chemical Industry.

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Glycaemia and body weight are regulated by sodium-glucose cotransporter 1 (SGLT1) expression via O-GlcNAcylation in the intestine

Cited by 10 publications

References 39 publications

Eugenol alleviates transmissible gastroenteritis virus-induced intestinal epithelial injury by regulating NF-κB signaling pathway

Eugenol alleviates transmissible gastroenteritis virus-induced intestinal epithelial injury by regulating NF-κB signaling pathway

Protein O-GlcNAcylation and the regulation of energy homeostasis: lessons from knock-out mouse models

Lead exposure aggravates glucose metabolism disorders through gut microbiota dysbiosis and intestinal barrier damage in high‐fat diet‐fed mice

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