Graphical Abstract
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Fructose and glucose are often widely used in food processing and may contribute to many metabolic diseases. To observe the effects of different doses of glucose and fructose on human metabolism and cellular communication, volunteers were given low, medium, and high doses of glucose and fructose. Serum cytokines, glucose, lactate, nicotinamide adenine dinucleotide (NADH) and metabolic enzymes were assayed, and central carbon metabolic pathway networks and cytokine communication networks were constructed. The results showed that the glucose and fructose groups basically maintained the trend of decreasing catabolism and increasing anabolism with increasing dose. Compared with glucose, low-dose fructose decreased catabolism and increased anabolism, significantly enhanced the expression of the inflammatory cytokine interferon-γ (IFN-γ), macrophage-derived chemokine (MDC), induced protein-10 (IP-10), and eotaxin, and significantly reduced the activity of isocitrate dehydrogenase (ICDH) and pyruvate dehydrogenase complexes (PDHC). Both medium and high doses of fructose increase catabolism and anabolism, and there are more cytokines and enzymes with significant changes. Furthermore, multiple cytokines and enzymes show strong relevance to metabolic regulation by altering the transcription and expression of enzymes in central carbon metabolic pathways. Therefore, excessive intake of fructose should be reduced to avoid excessive inflammatory responses, allergic reactions and autoimmune diseases.
K. Nasim, S. Mahdi, Z.K. Maryam, et al., Fructose and high fructose corn syrup: are they a two-edged sword? Int. J. Food Sci. Nutr. 72 (2021) 592-614. https://doi.org/10.1080/09637486.2020.1862068.
R.X. Wei, D.H. Deng, Y.Q. Teng, et al., Study on the effect of different types of sugar on lipid deposition in goose fatty liver, Poult. Sci. 101 (2022) 101729. https://doi.org/10.1016/j.psj.2022.101729.
M.V. Liberti, J.W. Locasale, Histone lactylation: a new role for glucose metabolism, Trends Biochem. Sci. 45 (2020) 179-182. https://doi.org/10.1016/j.tibs.2019.12.004.
J.W. Locasale, New concepts in feedback regulation of glucose metabolism, Curr. Opin. Struct. Biol. 8 (2018) 32-38. https://doi.org/10.1016/j.coisb.2017.11.005.
M.A. Herman, M.J. Birnbaum, Molecular aspects of fructose metabolism and metabolic disease, Cell Metab. 33 (2021) 2329-2354. https://doi.org/10.1016/j.cmet.2021.09.010.
M. Coronati, F. Baratta, D. Pastori, et al., Added fructose in non-alcoholic fatty liver disease and in metabolic syndrome: a narrative review, Nutrients 14 (2022) 1127. https://doi.org/10.3390/nu14061127.
V. Vallon, T. Nakagawa, Renal tubular handling of glucose and fructose in health and disease, Compr. Physiol. 12 (2021) 2995-3044. https://doi.org/10.1002/cphy.c210030.
M.L.C. Zentella, D.V. García, R.H. Muñoz, Ethanol metabolism in the liver, the induction of oxidant stress, and the antioxidant defense system, Antioxidants 11 (2022) 1258. https://doi.org/10.3390/antiox11071258.
J.M. Cavaillon, Exotoxins and endotoxins: inducers of inflammatory cytokines, Toxicon. 149 (2018). https://doi.org/10.1016/j.toxicon.2017.10.016.
H.H. Li, C. Chen, D.W. Wang, Inflammatory cytokines, immune cells, and organ interactions in heart failure, Front. Physiol. 12 (2021) 695047. https://doi.org/10.3389/fphys.2021.695047.
W.L. Qiao, W.J. Wang, E Laurenti, et al., Intercellular network structure and regulatory motifs in the human hematopoietic system, Mol. Syst. Biol. 10 (2014) 741. https://doi.org/10.15252/msb.20145141.
H. Pahwa, K. Sharan, Food and nutrition as modifiers of the immune system: a mechanistic overview, Trends Food Sci. Technol. 123 (2022) 393-403. https://doi.org/10.1016/j.tifs.2022.03.017.
E. De Paepe, L. Van Gijseghem, M. De Spiegeleer, et al., A systematic review of metabolic alterations underlying ige-mediated food allergy in children, Mol. Nutr. Food Res. 65 (2021) e2100536. https://doi.org/10.1002/mnfr.202100536.
M.D. Haggadone, J. Speth, H.S. Hong, et al., ATP citrate lyase links increases in glycolysis to diminished release of vesicular suppressor of cytokine signaling 3 by alveolar macrophages, Biochim. Biophys. Acta Mol. Basis. Dis. 1868 (2022) 166548. https://doi.org/10.1016/j.bbadis.2022.166458.
J.Y. Kim, B. Park, A. Bettaieb, et al., Pro-inflammatory cytokines increase glycolysis through upregulation of uncoupling protein and akt activation in colorectal cancer cells, FASEB J. 36 (2022). https://doi.org/10.1096/fasebj.2022.36.S1.R5921.
N. Khurana, H. Chauhan, P Khurana. Expression analysis of a heat-inducible, Myo-inositol-1-phosphate synthase (MIPS) gene from wheat and the alternatively spliced variants of rice and Arabidopsis, Plant Cell Rep. 31 (2012) 237-251. https://doi.org/10.1007/s00299-011-1160-5.
A. Martínez-Trujillo, J.S. Aranda, C. Gómez-Sánchez, et al., Constitutive and inducible pectinolytic enzymes from Aspergillus flavipes FP-500 and their modulation by pH and carbon source Enzimas pectinolíticas constitutivas e indutíveis de Aspergillus flavipes FP-500 e sua modulação pelo pH e fonte de carbono, Braz. J. Microbiol. 40 (2009) 40-47. https://doi.org/10.1590/S1517-83822009000100006.
M. Frericks, C. Esser, A toolbox of novel murine house-keeping genes identified by meta-analysis of large scale gene expression profiles, Biochim. Biophys. Acta Gene. Regul. Mech. 1779 (2008) 830-837. https://doi.org/10.1016/j.bbagrm.2008.08.007.
P.J. Gibbs, C. Cameron, L.C. Tan, et al., House keeping genes and gene expression analysis in transplant recipients: a note of caution, Transpl. Immunol. 12 (2003) 89-97. https://doi.org/10.1016/S0966-3274(03)00010-8.
D.J. Wu, D.E. Sanin, B. Everts, et al., Type 1 interferons induce changes in core metabolism that are critical for immune function, Immunity 44 (2016) 1325-1336. https://doi.org/10.1016/j.immuni.2016.06.006.
O.U. Kawalekar, R.S. O’Connor, J.A. Fraietta, et al., Distinct signaling of coreceptors regulates specific metabolism pathways and impacts memory development in CAR T Cells, Immunity 44 (2016) 380-390. https://doi.org/10.1016/j.immuni.2016.01.021.
X.R. Wang, L.Y. Zhu, X.Q. Li, et al., Effects of high fructose corn syrup on intestinal microbiota structure and obesity in mice, NPJ Sci. Food 6 (2022) 17. https://doi.org/10.1038/s41538-022-00133-7.
B. Hieronimus, V. Medici, A.A. Bremer, et al., Synergistic effects of fructose and glucose on lipoprotein risk factors for cardiovascular disease in young adults, Metabolism 112 (2020) 154356. https://doi.org/10.1016/j.metabol.2020.154356.
Y. Liu, J. Cheng, L.J. Wan,et al., Total and added sugar intakes are increasing among children and adolescents in China: findings from CHNS 1997–2011, Nutrients 14 (2022) 3340. https://doi.org/10.3390/nu14163340.
Y. Zhu, Y. Li, Y. Xu, et al., Development of bifunctional biosensors for sensing and dynamic control of glycolysis flux in metabolic engineering, Metab. 6 (2021) 142-151. https://doi.org/10.1016/j.ymben.2021.09.011.
B. Teusink, J. Passarge, C. A. Reijenga, et al., Can yeast glycolysis be understood in terms of in vitro kinetics of the constituent enzymes? Testing biochemistry, Eur. J. Med. Chem. 267 (2000) 5313-5329. https://doi.org/10.1046/j.1432-1327.2000.01527.x.
V.A. Pierce, D.L. Crawford, Rapid enzyme assays investigating the variation in the glycolytic pathway in field-caught populations of Fundulus heteroclitus, Biochem. 32 (1994) 315-330. https://doi.org/10.1007/PL00020710.
F. Yang, Y. Gong, N. Yu, et al., ST36 acupuncture alleviates the inflammation of adjuvant-induced arthritic rats by targeting monocyte/macrophage modulation, Evid. Based Complementary Altern. Med. 2021 (2021) 9430501. https://doi.org/10.1155/2021/9430501.
Y. Xu, S. Hong, X. Zhao, et al. Acupuncture alleviates rheumatoid arthritis by immune-network modulation, Am. J. Chinese Med. 46 (2018) 1-23. https://doi.org/10.1142/S0192415X18500520.
M.F. Hsieh, S.H. Sze, Finding alignments of conserved graphlets in protein interaction networks, J. Comput. Biol. 21 (2014) 234-246. https://doi.org/10.1089/cmb.2013.0130.
H. Wang, G. Pang, Effect of resistant and digestible rice starches on human cytokine and lactate metabolic networks in serum, Cytokine 93 (2017) 57-65. https://doi.org/10.1016/j.cyto.2017.05.009.
G. Altan-Bonnet, R. Mukherjee, Cytokine-mediated communication: a quantitative appraisal of immune complexity, Nat. Rev. Immunol. 19 (2019) 205-217. https://doi.org/10.1038/s41577-019-0131-x.
T. MariaArmineh, Z. Bruce, G. Ivan, The writers, readers, and erasers in redox regulation of GAPDH, Antioxidants 9 (2020) 1288. https://doi.org/10.3390/antiox9121288.
E.R. Chalhoub, J.M. Belovich, Quantitative analysis of the interaction of ethanol metabolism with gluconeogenesis and fatty acid oxidation in the perfused liver of fasted rats, Arch. Biochem. Biophys. 718 (2022) 109148. https://doi.org/10.1016/j.abb.2022.109148.
K. Barinova, M. Serebryakova, E. Sheval, et al., Modification by glyceraldehyde-3-phosphate prevents amyloid transformation of alpha-synuclein, Biochim Biophys Acta Proteins Proteom. 1867 (2019) 396-404. https://doi.org/10.1016/j.bbapap.2019.01.003.
O.A. Lozoya, I. Martinez-Reyes, T. Wang, et al., Mitochondrial nicotinamide adenine dinucleotide reduced (NADH) oxidation links the tricarboxylic acid (TCA) cycle with methionine metabolism and nuclear DNA methylation, PLoS Biol. 16 (2018) e2005707. https://doi.org/10.1371/journal.pbio.2005707.
J. Sun, J.B. Zhao, C. Sun, et al., Prenatal exposure of rats to staphylococcal enterotoxin B alters the expression of Th1 and Th2 cytokines via decreased methylation in the spleen of adult but not neonatal offspring, Iran. J. Immunol. 19 (2022) 3. https://doi.org/10.22034/IJI.2022.89946.1979.
C.H. Kuo, M.S. Lee, H.F. Kuo, et al., Azithromycin suppresses Th1- and Th2-related chemokines IP-10/MDC in human monocytic cell line, J. Microbiol. Immunol. Infect. 52 (2019) 872-879. https://doi.org/10.1016/j.jmii.2019.10.001.
V. Da C. Lisboa, M.R. Alves, R.Da S. Corrêa, et al., Predominance of Th1 immune response in pleural effusion of patients with tuberculosis among other exudative etiologies, J. Clin. Microbiol. 58(2019) e00927-19. https://doi.org/10.1128/JCM.00927-19.
W.Y. Yu, L.X. Ma, Y. Tian, et al., Acupuncture alleviates menstrual pain in rat model via suppressing eotaxin/CCR3 axis to weak EOS-MC activation, Evid. Based Complementary Altern. Med. 2022 (2022) 4571981. https://doi.org/10.1155/2022/4571981.
G. Fanelli, F. Benedetti, S.M. Wang, et al., Reduced CXCL1/GRO chemokine plasma levels are a possible biomarker of elderly depression, J. Affect. 249 (2019) 410-417. https://doi.org/10.1016/j.jad.2019.02.042.
S.R. Shah, S.B. Shaikh, Y.P. Bhandary, er al., Relevance of inflammatory cytokine mRNA expression of tumour necrosis factor-alpha (TNFα), interleukin 17A (IL 17A) and interleukin 6 (IL 6) in Indian patients with psoriasis, Indian dermatol, Online J. 13 (2022) 229-233. https://doi.org/10.4103/idoj.idoj_306_21.
S.J. Xing, S.L. Chen, X.L. Yang, et al., Role of MAPK activity in PD-L1 expression in hepatocellular carcinoma cells, J. BUON 25 (2020) 1875-1882.
K. Oda, Y. Matsuoka, A. Funahashi, et al., A comprehensive pathway map of epidermal growth factor receptor signaling, Mol. Syst. Biol. 1 (2005). https://doi.org/10.1038/msb4100014.
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