Fructose and Mannose in Inborn Errors of Metabolism and Cancer

Lieu, Elizabeth L.; Kelekar, Neil; Bhalla, Pratibha; Kim, Jiyeon

doi:10.3390/metabo11080479

Cited by 15 publications

(10 citation statements)

References 136 publications

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“…Since the observed number of differential genes in the rumen and ileum was small (Supplementary file 4), a further GSEA was conducted to detect subtle gene expression changes. Fructose and mannose metabolisms are vital in cellular productivity, complex cellular processes (e.g., glycosylation) and cellular health (Lieu et al, 2021). In the present study, the GSEA analysis showed that feeding silybum marianum meal to growing lambs upregulated some genes in the fructose and mannose metabolism pathway in the rumen.…”

Section: A B Figuresupporting

confidence: 53%

An integrated transcriptome and microbial community analysis reveals potential mechanisms for increased immune responses when replacing silybum marianum meal with soybean meal in growing lambs

Zhang

Ren²,

Gebeyew³

et al. 2023

Front. Microbiol.

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Silybum marianum meal is a by-product that remains silymarin complex and is perceived as a potential-protein source. The potential and its mechanism of silybum marianum meal as a protein supplement in ruminants were evaluated by testing the growth performance, biochemical parameters, cytokine levels, gut transcriptome and microbial community profiles. Forty-two male Hulunbeier growing lambs (aged about 3-month-old; averaged body weight of 21.55 kg) were randomly divided into the CON (with 10% soybean meal) and SIL groups (with 10% silybum marianum meal). There was no significant difference in growth performance, feed intakes, or serum biochemical parameters between CON and SIL. The serum levels of IL-1β, TNF-α, TGF-β, HGF, and VEGF were all increased (p < 0.05) in the SIL group as compared with the CON group. Transcriptome gene set enrichment analysis (GSEA) revealed that the core genes in the rumen from SIL group were enriched with fructose and mannose metabolism, while the core genes in the ileum were enriched for three biological process, including digestive tract development, positive regulation of MAPK cascade, and regulation of I-kappaB kinase/NF-kappaB signaling. The 16S rDNA results showed that the relative abundance of Bacteroidetes, Firmicutes, Synergistetes, and Verrucomicrobia in the rumen from SIL group was significantly higher than that in CON group (p < 0.05), whereas Proteobacteria was significantly lower than that in CON group (p < 0.05). The LEfSe analysis showed that the genera Pyramidobacter, Saccharofermentans, Anaerovibrio, Oscillibacter and Barnesiella were enriched in the rumen from SIL group, whereas Sharpea was enriched in the CON group (LDA > 2). In the ileum, there were no significant differences in the phylum-level classification of microbes observed. At the genus level, the relative abundances of Bifidobacterium and Ruminococcus in the ileum from SIL group were significantly higher than that in the CON group (p < 0.05), whereas the relative abundance of Clostridium_XI was lower (p < 0.05). Correlation analysis showed that Clostridium_XI was negatively correlated with VEGF, TGF-β, TNF-α and HGF (p < 0.05). Core genes BMP4 and CD4 were negatively correlated with Clostridium_XI (p < 0.05). Our results indicated that supplementing silybum marianum meal as a replacement for soybean meal resulted in increased cytokines production without affecting growth performance in growing lambs, and the enrichment of immune-related genes and altered microbial community in the ileum were contributed to the increased immune responses.

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Section: A B Figuresupporting

confidence: 53%

An integrated transcriptome and microbial community analysis reveals potential mechanisms for increased immune responses when replacing silybum marianum meal with soybean meal in growing lambs

Zhang

Ren²,

Gebeyew³

et al. 2023

Front. Microbiol.

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“…Osmolytes, such as sucrose, fructose, and mannose, are resources of energy, nutrition, structural materials, signaling molecules, and crucially contribute to seed germination and the growth of plantlets ( Osuna et al, 2015 ). Maize ( Zea mays L.) seedlings exposed to heat stress displayed sudden degradation of glycan contents and upregulated fructose and mannose metabolism ( Lieu et al, 2021 ). The expression of genes involved in fructose, mannose, and sucrose biosynthesis was also upregulated in 21-day-old maize seedlings exposed to heat stress ( Stavridou et al, 2021 ).…”

Section: Physiological Effects Of Heat Stressmentioning

confidence: 99%

Heat Stress-Mediated Constraints in Maize (Zea mays) Production: Challenges and Solutions

et al. 2022

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Graphical AbstractThis review summarized heat stress-mediated morphological and physiological changes in maize and elucidated the molecular mechanisms responsible for maize response to heat stress. Furthermore, plausible approaches to dissecting the regulatory network associated with heat stress response and improving maize adaptation to global warming have been discussed. This figure was made using BioRender.

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“…RNAi against Mpi (MPI), another gene in the GDP-mannose pathway, worsened the DPAGT1 and ER stress models (S7 Table ). However, MPI interconverts mannose-6-phosphate and fructose-6-phosphate [72], which means its inhibition could increase or decrease GDPmannose synthesis. Given that we also see differential effects of fructose in our two models, metabolomic analysis of these pathways may be required to understand the exact mechanism of Mpi loss under DPAGT1 impairment.…”

Section: Discussionmentioning

confidence: 99%

A genome-wide CRISPR screen identifies DPM1 as a modifier of DPAGT1 deficiency and ER stress

et al. 2022

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Partial loss-of-function mutations in glycosylation pathways underlie a set of rare diseases called Congenital Disorders of Glycosylation (CDGs). In particular, DPAGT1-CDG is caused by mutations in the gene encoding the first step in N-glycosylation, DPAGT1, and this disorder currently lacks effective therapies. To identify potential therapeutic targets for DPAGT1-CDG, we performed CRISPR knockout screens in Drosophila cells for genes associated with better survival and glycoprotein levels under DPAGT1 inhibition. We identified hundreds of candidate genes that may be of therapeutic benefit. Intriguingly, inhibition of the mannosyltransferase Dpm1, or its downstream glycosylation pathways, could rescue two in vivo models of DPAGT1 inhibition and ER stress, even though impairment of these pathways alone usually causes CDGs. While both in vivo models ostensibly cause cellular stress (through DPAGT1 inhibition or a misfolded protein), we found a novel difference in fructose metabolism that may indicate glycolysis as a modulator of DPAGT1-CDG. Our results provide new therapeutic targets for DPAGT1-CDG, include the unique finding of Dpm1-related pathways rescuing DPAGT1 inhibition, and reveal a novel interaction between fructose metabolism and ER stress.

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Fructose and Mannose in Inborn Errors of Metabolism and Cancer

Cited by 15 publications

References 136 publications

An integrated transcriptome and microbial community analysis reveals potential mechanisms for increased immune responses when replacing silybum marianum meal with soybean meal in growing lambs

An integrated transcriptome and microbial community analysis reveals potential mechanisms for increased immune responses when replacing silybum marianum meal with soybean meal in growing lambs

Heat Stress-Mediated Constraints in Maize (Zea mays) Production: Challenges and Solutions

A genome-wide CRISPR screen identifies DPM1 as a modifier of DPAGT1 deficiency and ER stress

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