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Accumulating clinical and experimental evidence shows that obesity, insulin resistance, and diabetes are accompanied by changes in sialic-acid levels. In these conditions, the sialic-acid axis is also broadly remodeled: writers (sialyltransferases), erasers (neuraminidases), and readers (Siglecs) are dysregulated across adipose tissue, liver, pancreas, endothelium, and blood, shifting insulin signaling and inflammatory tone. This review summarizes relevant studies from the perspectives of disease clinical indicators, molecular mechanisms, and interventions targeting sialic acid. Taken together, these results confirm that sialic acids and related molecules play important roles in multiple metabolic diseases; however, controversies remain due to differences in glycan structure, isoforms, and tissue specificity, particularly regarding the precise roles of neuraminidases. Future studies should build on advanced, standardized glycomic and glycoproteomic measures to define molecule- and tissue-specific roles of sialic acids in metabolic disease, enabling reliable biomarkers and guiding targeted therapy.<\/jats:p>","DOI":"10.3390\/biom15111522","type":"journal-article","created":{"date-parts":[[2025,10,29]],"date-time":"2025-10-29T05:48:46Z","timestamp":1761716926000},"page":"1522","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["The Emerging Role of Sialic Acids in Obesity and Diabetes: Molecular Mechanisms and Therapeutic Perspectives"],"prefix":"10.3390","volume":"15","author":[{"given":"Xinyi","family":"Peng","sequence":"first","affiliation":[{"name":"Department of Pharmacology, School of Medicine, Southern University of Science and Technology, Shenzhen 518055, China"},{"name":"Department of Rheumatism and Immunology, Peking University Shenzhen Hospital, Shenzhen 518036, China"},{"name":"Key University Laboratory of Metabolism and Health of Guangdong, Southern University of Science and Technology, Shenzhen 518055, China"},{"name":"The Key Laboratory of Inflammatory and Immunology Diseases, Shenzhen 518036, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Haojun","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, School of Medicine, Southern University of Science and Technology, Shenzhen 518055, China"},{"name":"Key University Laboratory of Metabolism and Health of Guangdong, Southern University of Science and Technology, Shenzhen 518055, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Qingwen","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Rheumatism and Immunology, Peking University Shenzhen Hospital, Shenzhen 518036, China"},{"name":"The Key Laboratory of Inflammatory and Immunology Diseases, Shenzhen 518036, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3335-6794","authenticated-orcid":false,"given":"Peng George","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, School of Medicine, Southern University of Science and Technology, Shenzhen 518055, China"},{"name":"Key University Laboratory of Metabolism and Health of Guangdong, Southern University of Science and Technology, Shenzhen 518055, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7409-7824","authenticated-orcid":false,"given":"Yang","family":"Ji","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, School of Medicine, Southern University of Science and Technology, Shenzhen 518055, China"},{"name":"Key University Laboratory of Metabolism and Health of Guangdong, Southern University of Science and Technology, Shenzhen 518055, China"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2025,10,29]]},"reference":[{"key":"ref_1","unstructured":"Varki, A., Cummings, R.D., Esko, J.D., Stanley, P., Hart, G.W., Aebi, M., Mohnen, D., Kinoshita, T., Packer, N.H., and Prestegard, J.H. (2022). Sialic Acids and Other Nonulosonic Acids. Essentials of Glycobiology, Cold Spring Harbor Laboratory Press."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/bs.accb.2018.09.001","article-title":"Exploration of the Sialic Acid World","volume":"Volume 75","author":"Schauer","year":"2018","journal-title":"Advances in Carbohydrate Chemistry and Biochemistry"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"3109","DOI":"10.1016\/j.cell.2021.04.023","article-title":"Small RNAs Are Modified with N-Glycans and Displayed on the Surface of Living Cells","volume":"184","author":"Flynn","year":"2021","journal-title":"Cell"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"784","DOI":"10.1038\/s41586-025-09310-6","article-title":"RNA N-Glycosylation Enables Immune Evasion and Homeostatic Efferocytosis","volume":"645","author":"Graziano","year":"2025","journal-title":"Nature"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"846","DOI":"10.1016\/j.cell.2023.12.033","article-title":"Cell Surface RNAs Control Neutrophil Recruitment","volume":"187","author":"Zhang","year":"2024","journal-title":"Cell"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"11736","DOI":"10.1073\/pnas.182257399","article-title":"Inactivation of CMP-N-Acetylneuraminic Acid Hydroxylase Occurred Prior to Brain Expansion during Human Evolution","volume":"99","author":"Chou","year":"2002","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"523","DOI":"10.1016\/j.it.2018.04.004","article-title":"The Glycoscience of Immunity","volume":"39","author":"Zhou","year":"2018","journal-title":"Trends Immunol."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"365","DOI":"10.1146\/annurev-immunol-102419-035900","article-title":"Siglecs as Immune Cell Checkpoints in Disease","volume":"38","author":"Duan","year":"2020","journal-title":"Annu. Rev. Immunol."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"7673","DOI":"10.1038\/ncomms8673","article-title":"9-O-Acetylation of Sialic Acids Is Catalysed by CASD1 via a Covalent Acetyl-Enzyme Intermediate","volume":"6","author":"Baumann","year":"2015","journal-title":"Nat. Commun."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"217","DOI":"10.1038\/s41573-020-00093-1","article-title":"The Clinical Impact of Glycobiology: Targeting Selectins, Siglecs and Mammalian Glycans","volume":"20","author":"Smith","year":"2021","journal-title":"Nat. Rev. Drug Discov."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"5828","DOI":"10.1021\/jacs.4c14454","article-title":"Sialylation Shields Glycoproteins from Oxidative Stress: Mechanistic Insights into Sialic Acid Oxidation and Structural Stability","volume":"147","author":"Wang","year":"2025","journal-title":"J. Am. Chem. Soc."},{"key":"ref_12","doi-asserted-by":"crossref","unstructured":"Zeng, J., Liu, Y., Dong, C., Chong, S., Liu, Y., Bian, Z., Chen, X., and Fan, S. (2025). Sialyltransferase ST3GAL4 Directs a Dual Mechanism to Promote Pancreatic Ductal Adenocarcinoma Progression by Regulating Endoplasmic Reticulum Stress and Mitochondrial Homeostasis. Biochim. Biophys. Acta Mol. Basis Dis., 1871.","DOI":"10.1016\/j.bbadis.2025.167900"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"5659","DOI":"10.1074\/jbc.RA117.001194","article-title":"The ST6Gal-I Sialyltransferase Protects Tumor Cells against Hypoxia by Enhancing HIF-1\u03b1 Signaling","volume":"293","author":"Jones","year":"2018","journal-title":"J. Biol. Chem."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"31","DOI":"10.3109\/10520295.2014.937744","article-title":"The Association of Total Sialic Acid and Malondialdehyde Levels with Metabolic and Anthropometric Variables in Obesity","volume":"90","author":"Yerlikaya","year":"2015","journal-title":"Biotech. Histochem."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"205","DOI":"10.1515\/JPEM.2007.20.2.205","article-title":"Serum Sialic Acid, Hs-CRP and Oxidative Stress Parameters in Obese Children","volume":"20","author":"Yilmaz","year":"2007","journal-title":"J. Pediatr. Endocrinol. Metab."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"65","DOI":"10.1016\/S0168-8227(00)00144-3","article-title":"Relation of Serum Total Sialic Acid Concentrations with Diabetic Complications and Cardiovascular Risk Factors in Kuwaiti Type 2 Diabetic Patients","volume":"50","author":"Abdella","year":"2000","journal-title":"Diabetes Res. Clin. Pract."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"139","DOI":"10.1159\/000334070","article-title":"The Association of Serum Sialic Acid with Carotid Intima-Media Thickness and Anthropometric and Metabolic Parameters in Obese Children and Adolescents","volume":"59","author":"Akin","year":"2011","journal-title":"Ann. Nutr. Metab."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"17","DOI":"10.1016\/j.dsx.2013.02.030","article-title":"Relationship of Raised Serum Total and Protein Bound Sialic Acid Levels with Hyperinsulinemia and Indices of Insulin Sensitivity and Insulin Resistance in Non-Diabetic Normotensive Obese Subjects","volume":"7","author":"Rajappa","year":"2013","journal-title":"Diabetes Metab. Syndr."},{"key":"ref_19","first-page":"170","article-title":"The Relationship between Serum Total Sialic Acid Levels and Adenosine Deaminase Activity in Obesity","volume":"27","author":"Kurtul","year":"2006","journal-title":"Saudi Med. J."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/S0009-8981(03)00011-1","article-title":"Serum Sialic Acid, a Reputed Cardiovascular Risk Factor, Is Related to Serum Leptin Concentrations in Fijians","volume":"331","author":"Crook","year":"2003","journal-title":"Clin. Chim. Acta"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"1004","DOI":"10.1038\/sj.ijo.0802711","article-title":"Elevated Sialic Acid, but Not CRP, Predicts Features of the Metabolic Syndrome Independently of BMI in Women","volume":"28","author":"Browning","year":"2004","journal-title":"Int. J. Obes. Relat. Metab. Disord."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"57","DOI":"10.2337\/diacare.16.1.57","article-title":"Elevated Serum Sialic Acid Concentration in NIDDM and Its Relationship to Blood Pressure and Retinopathy","volume":"16","author":"Crook","year":"1993","journal-title":"Diabetes Care"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"e1173","DOI":"10.1210\/clinem\/dgae296","article-title":"Associations of Plasma and Fecal Metabolites with Body Mass Index and Body Fat Distribution in Children","volume":"110","author":"Hong","year":"2024","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"ref_24","first-page":"199","article-title":"Relationship between Serum Sialic Acids, Sialic Acid-Rich Inflammation-Sensitive Proteins and Cell Damage in Patients with Acute Myocardial Infarction","volume":"44","author":"Sunar","year":"2006","journal-title":"Clin. Chem. Lab. Med."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"1293","DOI":"10.1038\/s41467-023-36759-8","article-title":"N-Acetylneuraminic Acid Links Immune Exhaustion and Accelerated Memory Deficit in Diet-Induced Obese Alzheimer\u2019s Disease Mouse Model","volume":"14","author":"Suzzi","year":"2023","journal-title":"Nat. Commun."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"714","DOI":"10.1038\/ijo.2010.171","article-title":"The Effects of Intermittent or Continuous Energy Restriction on Weight Loss and Metabolic Disease Risk Markers: A Randomized Trial in Young Overweight Women","volume":"35","author":"Harvie","year":"2011","journal-title":"Int. J. Obes."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"894","DOI":"10.1194\/jlr.P064816","article-title":"Disialylated Apolipoprotein C-III Proteoform Is Associated with Improved Lipids in Prediabetes and Type 2 Diabetes","volume":"57","author":"Koska","year":"2016","journal-title":"J. Lipid Res."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"3727","DOI":"10.1007\/s00394-021-02539-7","article-title":"Diet Affects Glycosylation of Serum Proteins in Women at Risk for Cardiometabolic Disease","volume":"60","author":"Kim","year":"2021","journal-title":"Eur. J. Nutr."},{"key":"ref_29","doi-asserted-by":"crossref","unstructured":"Ouyang, R., Zheng, S., Wang, X., Li, Q., Ding, J., Ma, X., Zhuo, Z., Li, Z., Xin, Q., and Lu, X. (2023). Crosstalk between Breast Milk N-Acetylneuraminic Acid and Infant Growth in a Gut Microbiota-Dependent Manner. Metabolites, 13.","DOI":"10.3390\/metabo13070846"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1007\/s00592-006-0202-x","article-title":"The Association of Serum Total Sialic Acid\/Total Protein Ratio with Diabetic Parameters in Young Type 1 Diabetic Patients","volume":"43","author":"Atabek","year":"2006","journal-title":"Acta Diabetol."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"119","DOI":"10.1016\/S0168-8227(99)00121-7","article-title":"Serum Sialic Acid in Young Type-1 Diabetic Patients","volume":"47","author":"Crook","year":"2000","journal-title":"Diabetes Res. Clin. Pract."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"638","DOI":"10.1016\/j.metabol.2003.11.013","article-title":"Association of Serum Sialic Acid with Cardiovascular Metabolic Risk Factors in Kuwaiti Children and Adolescents with Type 1 Diabetes","volume":"53","author":"Moussa","year":"2004","journal-title":"Metabolism"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"435","DOI":"10.2337\/diacare.19.5.435","article-title":"Raised Serum Sialic Acid Concentration Precedes Onset of Microalbuminuria in IDDM. A 10-Year Follow-up Study","volume":"19","author":"Yokoyama","year":"1996","journal-title":"Diabetes Care"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"1383","DOI":"10.1016\/0024-3205(95)02096-2","article-title":"Plasma Sialic Acid in Animal Models of Diabetes Mellitus: Evidence for Modulation of Sialic Acid Concentrations by Insulin Deficiency","volume":"57","author":"Pickup","year":"1995","journal-title":"Life Sci."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"5","DOI":"10.1038\/s43856-022-00231-3","article-title":"Identification of Serum Metabolome Signatures Associated with Retinal and Renal Complications of Type 2 Diabetes","volume":"3","author":"Tomofuji","year":"2023","journal-title":"Commun. Med."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"911","DOI":"10.2217\/bmm-2020-0776","article-title":"Sialic Acid As A Potential Biomarker for Cardiovascular Disease, Diabetes and Cancer","volume":"15","author":"Cheeseman","year":"2021","journal-title":"Biomark. Med."},{"key":"ref_37","unstructured":"Varki, A., Cummings, R.D., Esko, J.D., Stanley, P., Hart, G.W., Aebi, M., Mohnen, D., Kinoshita, T., Packer, N.H., and Prestegard, J.H. (2022). Glycosphingolipids. Essentials of Glycobiology, Cold Spring Harbor Laboratory Press."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"706","DOI":"10.1038\/ijo.2015.223","article-title":"GM3 Ganglioside and Phosphatidylethanolamine-Containing Lipids Are Adipose Tissue Markers of Insulin Resistance in Obese Women","volume":"40","author":"Wentworth","year":"2016","journal-title":"Int. J. Obes."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"3085","DOI":"10.1074\/jbc.M103705200","article-title":"Ganglioside GM3 Participates in the Pathological Conditions of Insulin Resistance","volume":"277","author":"Tagami","year":"2002","journal-title":"J. Biol. Chem."},{"key":"ref_40","doi-asserted-by":"crossref","unstructured":"Inokuchi, J.-I., and Kanoh, H. (2022). Pathophysiological Significance of GM3 Ganglioside Molecular Species with a Particular Attention to the Metabolic Syndrome Focusing on Toll-Like Receptor 4 Binding. Front. Mol. Biosci., 9.","DOI":"10.3389\/fmolb.2022.918346"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"1742","DOI":"10.1016\/j.cellsig.2015.05.010","article-title":"NEU3 Sialidase as a Marker of Insulin Sensitivity: Regulation by Fatty Acids","volume":"27","author":"Lipina","year":"2015","journal-title":"Cell Signal"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"141","DOI":"10.1074\/mcp.M115.054221","article-title":"Terminal Galactosylation and Sialylation Switching on Membrane Glycoproteins upon TNF-Alpha-Induced Insulin Resistance in Adipocytes","volume":"15","author":"Parker","year":"2016","journal-title":"Mol. Cell Proteom."},{"key":"ref_43","doi-asserted-by":"crossref","unstructured":"Vattepu, R., Sneed, S.L., and Anthony, R.M. (2022). Sialylation as an Important Regulator of Antibody Function. Front. Immunol., 13.","DOI":"10.3389\/fimmu.2022.818736"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"100002","DOI":"10.1016\/j.glycos.2025.100002","article-title":"The Importance of IgG N-Glycosylation in Health, Disease, and Neonatal Hemochromatosis","volume":"1","author":"Anthony","year":"2025","journal-title":"Glycosci. Ther."},{"key":"ref_45","doi-asserted-by":"crossref","unstructured":"Plomp, R., Ruhaak, L.R., Uh, H.-W., Reiding, K.R., Selman, M., Houwing-Duistermaat, J.J., Slagboom, P.E., Beekman, M., and Wuhrer, M. (2017). Subclass-Specific IgG Glycosylation Is Associated with Markers of Inflammation and Metabolic Health. Sci. Rep., 7.","DOI":"10.1038\/s41598-017-12495-0"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"110","DOI":"10.1016\/j.imbio.2018.10.002","article-title":"Increased Central Adiposity Is Associated with Pro-Inflammatory Immunoglobulin G N-Glycans","volume":"224","author":"Russell","year":"2019","journal-title":"Immunobiology"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"309","DOI":"10.1172\/JCI89333","article-title":"Hyposialylated IgG Activates Endothelial IgG Receptor Fc\u03b3RIIB to Promote Obesity-Induced Insulin Resistance","volume":"128","author":"Tanigaki","year":"2018","journal-title":"J. Clin. Investig."},{"key":"ref_48","doi-asserted-by":"crossref","unstructured":"\u0160imuni\u0107-Bri\u0161ki, N., Zeki\u0107, R., Dukari\u0107, V., O\u010di\u0107, M., Frkatovi\u0107-Hod\u017ei\u0107, A., Deri\u0161, H., Lauc, G., and Knjaz, D. (2023). Physical Exercise Induces Significant Changes in Immunoglobulin G N-Glycan Composition in a Previously Inactive, Overweight Population. Biomolecules, 13.","DOI":"10.3390\/biom13050762"},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"1521","DOI":"10.1038\/s41366-021-00816-3","article-title":"Extensive Weight Loss Reduces Glycan Age by Altering IgG N-Glycosylation","volume":"45","author":"Greto","year":"2021","journal-title":"Int. J. Obes."},{"key":"ref_50","doi-asserted-by":"crossref","unstructured":"Deri\u0161, H., Tominac, P., Vu\u010dkovi\u0107, F., Bri\u0161ki, N., Astrup, A., Blaak, E.E., Lauc, G., and Gudelj, I. (2022). Effects of Low-Calorie and Different Weight-Maintenance Diets on IgG Glycome Composition. Front. Immunol., 13.","DOI":"10.3389\/fimmu.2022.995186"},{"key":"ref_51","doi-asserted-by":"crossref","unstructured":"Tijardovi\u0107, M., Marijan\u010devi\u0107, D., Bok, D., Kifer, D., Lauc, G., Gornik, O., and Keser, T. (2019). Intense Physical Exercise Induces an Anti-Inflammatory Change in IgG N-Glycosylation Profile. Front. Physiol., 10.","DOI":"10.3389\/fphys.2019.01522"},{"key":"ref_52","doi-asserted-by":"crossref","unstructured":"Sarin, H.V., Gudelj, I., Honkanen, J., Ihalainen, J.K., Vuorela, A., Lee, J.H., Jin, Z., Terwilliger, J.D., Isola, V., and Ahtiainen, J.P. (2019). Molecular Pathways Mediating Immunosuppression in Response to Prolonged Intensive Physical Training, Low-Energy Availability, and Intensive Weight Loss. Front. Immunol., 10.","DOI":"10.3389\/fimmu.2019.00907"},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"2278","DOI":"10.1074\/jbc.M116.747667","article-title":"The Inhibitory Role of A2,6-Sialylation in Adipogenesis","volume":"292","author":"Kaburagi","year":"2017","journal-title":"J. Biol. Chem."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"15","DOI":"10.1016\/j.diff.2016.08.003","article-title":"Heparan Sulfates and the Decrease of N-Glycans Promote Early Adipogenic Differentiation Rather than Myogenesis of Murine Myogenic Progenitor Cells","volume":"93","author":"Grassot","year":"2017","journal-title":"Differentiation"},{"key":"ref_55","first-page":"293","article-title":"Alterations of Protein Glycosylation in Embryonic Stem Cells during Adipogenesis","volume":"41","author":"Liu","year":"2018","journal-title":"Int. J. Mol. Med."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"857","DOI":"10.1016\/j.ijbiomac.2020.01.123","article-title":"Diversity of Sialidases Found in the Human Body\u2014A Review","volume":"148","author":"Frecer","year":"2020","journal-title":"Int. J. Biol. Macromol."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"3002","DOI":"10.1021\/acs.jmedchem.1c01612","article-title":"Human Neuraminidases: Structures and Stereoselective Inhibitors","volume":"65","author":"Bourguet","year":"2022","journal-title":"J. Med. Chem."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"28430","DOI":"10.1074\/jbc.M109.031419","article-title":"Heterodimerization of the Sialidase NEU1 with the Chaperone Protective Protein\/Cathepsin A Prevents Its Premature Oligomerization","volume":"284","author":"Bonten","year":"2009","journal-title":"J. Biol. Chem."},{"key":"ref_59","doi-asserted-by":"crossref","unstructured":"Toussaint, K., Appert-Collin, A., Morjani, H., Albrecht, C., Sartelet, H., Romier-Crouzet, B., Maurice, P., Duca, L., Blaise, S., and Bennasroune, A. (2022). Neuraminidase-1: A Sialidase Involved in the Development of Cancers and Metabolic Diseases. Cancers, 14.","DOI":"10.3390\/cancers14194868"},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"1027","DOI":"10.1248\/bpb.b12-00995","article-title":"Acidic Sialidase Activity Is Aberrant in Obese and Diabetic Mice","volume":"36","author":"Natori","year":"2013","journal-title":"Biol. Pharm. Bull."},{"key":"ref_61","first-page":"10072","article-title":"MicroRNA-205 Ameliorates Lipid Accumulation in Non-Alcoholic Fatty Liver Disease through Targeting NEU1","volume":"23","author":"Hu","year":"2019","journal-title":"Eur. Rev. Med. Pharmacol. Sci."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"2338","DOI":"10.2337\/db12-1825","article-title":"Positive Regulation of Insulin Signaling by Neuraminidase 1","volume":"62","author":"Dridi","year":"2013","journal-title":"Diabetes"},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"76","DOI":"10.1016\/j.molmet.2018.03.017","article-title":"Neuraminidase 1 Activates Insulin Receptor and Reverses Insulin Resistance in Obese Mice","volume":"12","author":"Fougerat","year":"2018","journal-title":"Mol. Metab."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"603","DOI":"10.1093\/glycob\/cwq010","article-title":"Desialylation of Insulin Receptors and IGF-1 Receptors by Neuraminidase-1 Controls the Net Proliferative Response of L6 Myoblasts to Insulin","volume":"20","author":"Arabkhari","year":"2010","journal-title":"Glycobiology"},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"3807","DOI":"10.2337\/db13-0508","article-title":"Elastin-Derived Peptides Are New Regulators of Insulin Resistance Development in Mice","volume":"62","author":"Blaise","year":"2013","journal-title":"Diabetes"},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"3221","DOI":"10.1016\/j.febslet.2015.09.018","article-title":"Ganglioside GM3 as a Gatekeeper of Obesity-Associated Insulin Resistance: Evidence and Mechanisms","volume":"589","author":"Lipina","year":"2015","journal-title":"FEBS Lett."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"27896","DOI":"10.1074\/jbc.M212200200","article-title":"Overexpression of Plasma Membrane-Associated Sialidase Attenuates Insulin Signaling in Transgenic Mice","volume":"278","author":"Sasaki","year":"2003","journal-title":"J. Biol. Chem."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"420","DOI":"10.1016\/j.metabol.2006.10.027","article-title":"Increased Hepatic Expression of Ganglioside-Specific Sialidase, NEU3, Improves Insulin Sensitivity and Glucose Tolerance in Mice","volume":"56","author":"Yoshizumi","year":"2007","journal-title":"Metabolism"},{"key":"ref_69","doi-asserted-by":"crossref","unstructured":"Minami, A., Fujita, Y., Shimba, S., Shiratori, M., Kaneko, Y.K., Sawatani, T., Otsubo, T., Ikeda, K., Kanazawa, H., and Mikami, Y. (2020). The Sialidase Inhibitor 2,3-Dehydro-2-Deoxy-N-Acetylneuraminic Acid Is a Glucose-Dependent Potentiator of Insulin Secretion. Sci. Rep., 10.","DOI":"10.1038\/s41598-020-62203-8"},{"key":"ref_70","doi-asserted-by":"crossref","unstructured":"Pilling, D., Martinez, T.C., and Gomer, R.H. (2024). Inhibition of CCl4-Induced Liver Inflammation and Fibrosis by a NEU3 Inhibitor. PLoS ONE, 19.","DOI":"10.1371\/journal.pone.0308060"},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"1298","DOI":"10.1038\/nm.4412","article-title":"Activation of Intestinal Hypoxia-Inducible Factor 2\u03b1 during Obesity Contributes to Hepatic Steatosis","volume":"23","author":"Xie","year":"2017","journal-title":"Nat. Med."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"107883","DOI":"10.1016\/j.isci.2023.107883","article-title":"Innate Mechanism of Mucosal Barrier Erosion in the Pathogenesis of Acquired Colitis","volume":"26","author":"Yang","year":"2023","journal-title":"iScience"},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"e2100937118","DOI":"10.1073\/pnas.2100937118","article-title":"Neu3 Neuraminidase Induction Triggers Intestinal Inflammation and Colitis in a Model of Recurrent Human Food-Poisoning","volume":"118","author":"Yang","year":"2021","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_74","doi-asserted-by":"crossref","unstructured":"Oh, M., Ha, D.-I., Son, C., Kang, J.G., Hwang, H., Moon, S.B., Kim, M., Nam, J., Kim, J.S., and Song, S.Y. (2022). Defect in Cytosolic Neu2 Sialidase Abrogates Lipid Metabolism and Impairs Muscle Function in Vivo. Sci. Rep., 12.","DOI":"10.1038\/s41598-022-07033-6"},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"345","DOI":"10.1016\/j.ejphar.2018.11.014","article-title":"Sialidase Activity in Human Pathologies","volume":"842","author":"Glanz","year":"2019","journal-title":"Eur. J. Pharmacol."},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"887","DOI":"10.1007\/s00253-012-4040-1","article-title":"Sialic Acid Metabolism and Sialyltransferases: Natural Functions and Applications","volume":"94","author":"Li","year":"2012","journal-title":"Appl. Microbiol. Biotechnol."},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"7207","DOI":"10.1073\/pnas.1523968113","article-title":"B-Cell-Independent Sialylation of IgG","volume":"113","author":"Jones","year":"2016","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"346","DOI":"10.1093\/glycob\/cwz096","article-title":"Modulation of Hepatocyte Sialylation Drives Spontaneous Fatty Liver Disease and Inflammation","volume":"30","author":"Oswald","year":"2020","journal-title":"Glycobiology"},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"129","DOI":"10.1093\/glycob\/cww098","article-title":"Mice Lacking Sialyltransferase ST3Gal-II Develop Late-Onset Obesity and Insulin Resistance","volume":"27","author":"Lopez","year":"2017","journal-title":"Glycobiology"},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"5152","DOI":"10.1111\/febs.16076","article-title":"Homeostatic and Pathogenic Roles of the GM3 Ganglioside","volume":"289","author":"Inokuchi","year":"2022","journal-title":"FEBS J."},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"1472","DOI":"10.1194\/jlr.M085753","article-title":"Deficient Ganglioside Synthesis Restores Responsiveness to Leptin and Melanocortin Signaling in Obese KKAy Mice","volume":"59","author":"Inamori","year":"2018","journal-title":"J. Lipid Res."},{"key":"ref_82","doi-asserted-by":"crossref","unstructured":"Strekalova, T., Veniaminova, E., Svirin, E., Kopeikina, E., Veremeyko, T., Yung, A.W.Y., Proshin, A., Tan, S.Z.K., Khairuddin, S., and Lim, L.W. (2021). Sex-Specific ADHD-like Behaviour, Altered Metabolic Functions, and Altered EEG Activity in Sialyltransferase ST3GAL5-Deficient Mice. Biomolecules, 11.","DOI":"10.3390\/biom11121759"},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"1446","DOI":"10.1038\/jid.2013.532","article-title":"Ganglioside GM3 Depletion Reverses Impaired Wound Healing in Diabetic Mice by Activating IGF-1 and Insulin Receptors","volume":"134","author":"Wang","year":"2014","journal-title":"J. Investig. Dermatol."},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"5573","DOI":"10.1073\/pnas.1505951112","article-title":"siRNA-Based Spherical Nucleic Acids Reverse Impaired Wound Healing in Diabetic Mice by Ganglioside GM3 Synthase Knockdown","volume":"112","author":"Randeria","year":"2015","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"e181207","DOI":"10.1172\/JCI181207","article-title":"ST8Sia6 Overexpression Protects Pancreatic \u03b2 Cells from Spontaneous Autoimmune Diabetes in Nonobese Diabetic Mice","volume":"135","author":"Choe","year":"2025","journal-title":"J. Clin. Investig."},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"3071","DOI":"10.4049\/jimmunol.2000023","article-title":"Cutting Edge: ST8Sia6-Generated \u03b1-2,8-Disialic Acids Mitigate Hyperglycemia in Multiple Low-Dose Streptozotocin-Induced Diabetes","volume":"204","author":"Belmonte","year":"2020","journal-title":"J. Immunol."},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"11756","DOI":"10.1038\/ncomms11756","article-title":"Human Islets Contain Four Distinct Subtypes of \u03b2 Cells","volume":"7","author":"Dorrell","year":"2016","journal-title":"Nat. Commun."},{"key":"ref_88","doi-asserted-by":"crossref","unstructured":"Gonzalez, Y., Herrera, M.T., Soldevila, G., Garcia-Garcia, L., Fabi\u00e1n, G., P\u00e9rez-Armendariz, E.M., Bobadilla, K., Guzm\u00e1n-Beltr\u00e1n, S., Sada, E., and Torres, M. (2012). High Glucose Concentrations Induce TNF-\u03b1 Production through the down-Regulation of CD33 in Primary Human Monocytes. BMC Immunol., 13.","DOI":"10.1186\/1471-2172-13-19"},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"946","DOI":"10.1038\/s41419-021-04217-2","article-title":"Diet-Induced Obesity Accelerates Oral Carcinogenesis by Recruitment and Functional Enhancement of Myeloid-Derived Suppressor Cells","volume":"12","author":"Peng","year":"2021","journal-title":"Cell Death Dis."},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"215918","DOI":"10.1016\/j.canlet.2022.215918","article-title":"Obesity Accelerates Immune Evasion of Non-Small Cell Lung Carcinoma via TFEB-Dependent Upregulation of Siglec-15 and Glycolytic Reprogramming","volume":"550","author":"Zhang","year":"2022","journal-title":"Cancer Lett."},{"key":"ref_91","doi-asserted-by":"crossref","unstructured":"Naujoks, W., Quandt, D., Hauffe, A., Kielstein, H., B\u00e4hr, I., and Spielmann, J. (2020). Characterization of Surface Receptor Expression and Cytotoxicity of Human NK Cells and NK Cell Subsets in Overweight and Obese Humans. Front. Immunol., 11.","DOI":"10.3389\/fimmu.2020.573200"},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"1017","DOI":"10.1007\/s12026-017-8942-y","article-title":"Siglec-7 Expression Is Reduced on a Natural Killer (NK) Cell Subset of Obese Humans","volume":"65","author":"Rosenstock","year":"2017","journal-title":"Immunol. Res."},{"key":"ref_93","doi-asserted-by":"crossref","unstructured":"Dharmadhikari, G., Stolz, K., Hauke, M., Morgan, N.G., Varki, A., De Koning, E., Kelm, S., and Maedler, K. (2017). Siglec-7 Restores \u03b2-Cell Function and Survival and Reduces Inflammation in Pancreatic Islets from Patients with Diabetes. Sci. Rep., 7.","DOI":"10.1038\/srep45319"},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"189","DOI":"10.1016\/j.lfs.2018.11.049","article-title":"Immunoregulatory Siglec Ligands Are Abundant in Human and Mouse Aorta and Are Up-Regulated by High Glucose","volume":"216","author":"Zhang","year":"2019","journal-title":"Life Sci."},{"key":"ref_95","doi-asserted-by":"crossref","unstructured":"Rakib, A., Mandal, M., Al Mamun, M.A., Kiran, S., Yasmen, N., Li, L., Collier, D.M., Jiang, J., Park, F., and Singh, U.P. (2025). Siglec-E Augments Adipose Tissue Inflammation by Modulating TRAF3 Signaling and Monocytic Myeloid-Derived Suppressor Cells during Obesity. Front. Immunol., 16.","DOI":"10.3389\/fimmu.2025.1501307"},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"1088","DOI":"10.1016\/j.cmet.2022.07.005","article-title":"CD24-Siglec Axis Is an Innate Immune Checkpoint against Metaflammation and Metabolic Disorder","volume":"34","author":"Wang","year":"2022","journal-title":"Cell Metab."},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"623","DOI":"10.1007\/s00125-024-06098-4","article-title":"A Novel Subpopulation of Monocytes with a Strong Interferon Signature Indicated by SIGLEC-1 Is Present in Patients with in Recent-Onset Type 1 Diabetes","volume":"67","author":"Guo","year":"2024","journal-title":"Diabetologia"},{"key":"ref_98","doi-asserted-by":"crossref","first-page":"49","DOI":"10.1016\/j.trsl.2024.09.003","article-title":"Siglec-5 as a Novel Receptor Mediates Endothelial Cells oxLDL Transcytosis to Promote Atherosclerosis","volume":"274","author":"Jia","year":"2024","journal-title":"Transl. Res."},{"key":"ref_99","doi-asserted-by":"crossref","unstructured":"Li, J., Yang, X., Wang, X., Jia, X., Wang, Z., Deng, A., Bai, X., Zhu, L., Li, B., and Feng, Z. (2017). Siglec-5 Is a Novel Marker of Critical Limb Ischemia in Patients with Diabetes. Sci. Rep., 7.","DOI":"10.1038\/s41598-017-11820-x"},{"key":"ref_100","doi-asserted-by":"crossref","unstructured":"Yida, Z., Imam, M.U., Ismail, M., Ismail, N., Ideris, A., and Abdullah, M.A. (2015). High Fat Diet-Induced Inflammation and Oxidative Stress Are Attenuated by N-Acetylneuraminic Acid in Rats. J. Biomed. Sci., 22.","DOI":"10.1186\/s12929-015-0211-6"},{"key":"ref_101","doi-asserted-by":"crossref","first-page":"550","DOI":"10.1089\/jmf.2023.K.0016","article-title":"Antiobesity Effect of N-Acetylneuraminic Acid by Enhancing Antioxidative Capacity in Mice Fed a High-Fat Diet","volume":"26","author":"Kaburagi","year":"2023","journal-title":"J. Med. Food"},{"key":"ref_102","doi-asserted-by":"crossref","first-page":"2005","DOI":"10.1161\/CIRCULATIONAHA.119.043490","article-title":"Supplementation with the Sialic Acid Precursor N-Acetyl-D-Mannosamine Breaks the Link Between Obesity and Hypertension","volume":"140","author":"Peng","year":"2019","journal-title":"Circulation"},{"key":"ref_103","doi-asserted-by":"crossref","first-page":"109875","DOI":"10.1016\/j.foodres.2020.109875","article-title":"A Comprehensive Review of Edible Bird\u2019s Nest","volume":"140","author":"Dai","year":"2021","journal-title":"Food Res. Int."},{"key":"ref_104","doi-asserted-by":"crossref","first-page":"7577","DOI":"10.1039\/D4FO00563E","article-title":"Edible Bird\u2019s Nest Regulates Glucose and Lipid Metabolic Disorders via the Gut-Liver Axis in Obese Mice","volume":"15","author":"Zhang","year":"2024","journal-title":"Food Funct."},{"key":"ref_105","doi-asserted-by":"crossref","unstructured":"Murugan, D.D., Md Zain, Z., Choy, K.W., Zamakshshari, N.H., Choong, M.J., Lim, Y.M., and Mustafa, M.R. (2020). Edible Bird\u2019s Nest Protects Against Hyperglycemia-Induced Oxidative Stress and Endothelial Dysfunction. Front. Pharmacol., 10.","DOI":"10.3389\/fphar.2019.01624"},{"key":"ref_106","doi-asserted-by":"crossref","unstructured":"Yida, Z., Imam, M.U., Ismail, M., Hou, Z., Abdullah, M.A., Ideris, A., and Ismail, N. (2015). Edible Bird\u2019s Nest Attenuates High Fat Diet-Induced Oxidative Stress and Inflammation via Regulation of Hepatic Antioxidant and Inflammatory Genes. BMC Complement. Altern. Med., 15.","DOI":"10.1186\/s12906-015-0843-9"},{"key":"ref_107","doi-asserted-by":"crossref","first-page":"131","DOI":"10.1016\/j.ajpath.2020.09.011","article-title":"High-Fat Diet-Induced Adipose Tissue and Liver Inflammation and Steatosis in Mice Are Reduced by Inhibiting Sialidases","volume":"191","author":"Pilling","year":"2021","journal-title":"Am. J. Pathol."}],"container-title":["Biomolecules"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2218-273X\/15\/11\/1522\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,29]],"date-time":"2025-10-29T06:20:37Z","timestamp":1761718837000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2218-273X\/15\/11\/1522"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,10,29]]},"references-count":107,"journal-issue":{"issue":"11","published-online":{"date-parts":[[2025,11]]}},"alternative-id":["biom15111522"],"URL":"https:\/\/doi.org\/10.3390\/biom15111522","relation":{},"ISSN":["2218-273X"],"issn-type":[{"value":"2218-273X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,10,29]]}}}