Fasting-Induced Upregulation of MKP-1 Modulates the Hepatic Response to Feeding

Sellers, Jacob; Brooks, Abigail; Fernando, Savanie; Westenberger, Gabrielle; Junkins, Sadie; Smith, Shauri; Min, Kisuk; Lawan, Ahmed

doi:10.3390/nu13113941

Cited by 3 publications

(2 citation statements)

References 30 publications

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“…Notably, it has been reported that DUSP-1 is involved in the control of energy expenditure, body mass, gluconeogenesis and insulin resistance onset by counteracting MAPK-dependent signals [ 80 , 86 , 87 ].…”

Section: Discussionmentioning

confidence: 99%

TFEB inhibition induces melanoma shut-down by blocking the cell cycle and rewiring metabolism

et al. 2023

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Melanomas are characterised by accelerated cell proliferation and metabolic reprogramming resulting from the contemporary dysregulation of the MAPK pathway, glycolysis and the tricarboxylic acid (TCA) cycle. Here, we suggest that the oncogenic transcription factor EB (TFEB), a key regulator of lysosomal biogenesis and function, controls melanoma tumour growth through a transcriptional programme targeting ERK1/2 activity and glucose, glutamine and cholesterol metabolism. Mechanistically, TFEB binds and negatively regulates the promoter of DUSP-1, which dephosphorylates ERK1/2. In melanoma cells, TFEB silencing correlates with ERK1/2 dephosphorylation at the activation-related p-Thr185 and p-Tyr187 residues. The decreased ERK1/2 activity synergises with TFEB control of CDK4 expression, resulting in cell proliferation blockade. Simultaneously, TFEB rewires metabolism, influencing glycolysis, glucose and glutamine uptake, and cholesterol synthesis. In TFEB-silenced melanoma cells, cholesterol synthesis is impaired, and the uptake of glucose and glutamine is inhibited, leading to a reduction in glycolysis, glutaminolysis and oxidative phosphorylation. Moreover, the reduction in TFEB level induces reverses TCA cycle, leading to fatty acid production. A syngeneic BRAFV600E melanoma model recapitulated the in vitro study results, showing that TFEB silencing sustains the reduction in tumour growth, increase in DUSP-1 level and inhibition of ERK1/2 action, suggesting a pivotal role for TFEB in maintaining proliferative melanoma cell behaviour and the operational metabolic pathways necessary for meeting the high energy demands of melanoma cells.

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Section: Discussionmentioning

confidence: 99%

TFEB inhibition induces melanoma shut-down by blocking the cell cycle and rewiring metabolism

et al. 2023

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“…Gut microbiota have been described as a new metabolic organ that participates in regulating host metabolism ( 12 , 13 ). Accumulating evidence suggests that changes in metabolic levels can affect health status and are correlated with some diseases, such as Type 2 diabetes ( 14 ), pulmonary tuberculosis ( 15 ), obesity ( 16 ), epilepsy ( 17 ), and others. Recent studies have reported that both environmental and host factors, such as environmental contaminants ( 18 ), lifestyle ( 19 ), disease conditions ( 20 ), and drug use ( 21 ), could all influence gut metabolism.…”

Section: Introductionmentioning

confidence: 99%

Shifts in Fecal Metabolite Profiles Associated With Ramadan Fasting Among Chinese and Pakistani Individuals

Chen

Ikram

et al. 2022

Front. Nutr.

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The human gut microbiota has been proposed to serve as a multifunctional organ in host metabolism, contributing effects to nutrient acquisition, immune response, and digestive health. Fasting during Ramadan may alter the composition of gut microbiota through changes in dietary behavior, which ultimately affects the contents of various metabolites in the gut. Here, we used liquid chromatography–mass spectrometry-based metabolomics to investigate the composition of fecal metabolites in Chinese and Pakistani individuals before and after Ramadan fasting. Principal component analysis showed distinct separation of metabolite profiles among ethnic groups as well as between pre- and post-fasting samples. After Ramadan fasting, the Chinese and Pakistani groups showed significant differences in their respective contents of various fecal metabolites. In particular, L-histidine, lycofawcine, and cordycepin concentrations were higher after Ramadan fasting in the Chinese group, while brucine was enriched in the Pakistani group. The KEGG analysis suggested that metabolites related to purine metabolism, 2-oxocarboxylic acid metabolism, and lysine degradation were significantly enriched in the total subject population pre-fasting vs. post-fasting comparisons. Several bacterial taxa were significantly correlated with specific metabolites unique to each ethnic group, suggesting that changes in fecal metabolite profiles related to Ramadan fasting may be influenced by associated shifts in gut microbiota. The fasting-related differences in fecal metabolite profile, together with these group-specific correlations between taxa and metabolites, support our previous findings that ethnic differences in dietary composition also drive variation in gut microbial composition and diversity. This landscape view of interconnected dietary behaviors, microbiota, and metabolites contributes to the future development of personalized, diet-based therapeutic strategies for gut-related disorders.

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Genetic polymorphisms of PKLR gene and their associations with milk production traits in Chinese Holstein cows

Zhao²,

Liu

et al. 2022

Front. Genet.

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Our previous work had confirmed that pyruvate kinase L/R (PKLR) gene was expressed differently in different lactation periods of dairy cattle, and participated in lipid metabolism through insulin, PI3K-Akt, MAPK, AMPK, mTOR, and PPAR signaling pathways, suggesting that PKLR is a candidate gene to affect milk production traits in dairy cattle. Here, we verified whether this gene has significant genetic association with milk yield and composition traits in a Chinese Holstein cow population. In total, we identified 21 single nucleotide polymorphisms (SNPs) by resequencing the entire coding region and partial flanking region of PKLR gene, in which, two SNPs were located in 5′ promoter region, two in 5′ untranslated region (UTR), three in introns, five in exons, six in 3′ UTR and three in 3′ flanking region. The single marker association analysis displayed that all SNPs were significantly associated with milk yield, fat and protein yields or protein percentage (p ≤ 0.0497). The haplotype block containing all the SNPs, predicted by Haploview, had a significant association with fat yield and protein percentage (p ≤ 0.0145). Further, four SNPs in 5′ regulatory region and eight SNPs in UTR and exon regions were predicted to change the transcription factor binding sites (TFBSs) and mRNA secondary structure, respectively, thus affecting the expression of PKLR, leading to changes in milk production phenotypes, suggesting that these SNPs might be the potential functional mutations for milk production traits in dairy cattle. In conclusion, we demonstrated that PKLR had significant genetic effects on milk production traits, and the SNPs with significant genetic effects could be used as candidate genetic markers for genomic selection (GS) in dairy cattle.

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Fasting-Induced Upregulation of MKP-1 Modulates the Hepatic Response to Feeding

Cited by 3 publications

References 30 publications

TFEB inhibition induces melanoma shut-down by blocking the cell cycle and rewiring metabolism

TFEB inhibition induces melanoma shut-down by blocking the cell cycle and rewiring metabolism

Shifts in Fecal Metabolite Profiles Associated With Ramadan Fasting Among Chinese and Pakistani Individuals

Genetic polymorphisms of PKLR gene and their associations with milk production traits in Chinese Holstein cows

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