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This study aimed to explore the molecular mechanisms underlying the effects of semaglutide on lipid metabolism in visceral white adipose tissue in a mouse model of T2DM.Methods:Male C57BL\/6J mice were given a normal diet, a high-fat diet with streptozotocin, or a high-fat diet with semaglutide. Blood samples, liver tissue, and adipose tissue were collected for analysis. Serum adipokines, inflammatory cytokines, liver function, and lipid profiles were assessed. White adipose tissue and liver sections were processed for hematoxylin and eosin (H&amp;E) staining or immunohistochemistry (IHC) staining for the macrophage marker F4\/80. High-throughput targeted lipidomic analysis of epididymal white adipose tissue from these animals was performed using liquid chromatography-tandem mass spectrometry to characterize changes in lipid composition and function. Furthermore, the expression of genes related to adipokines, inflammation, and lipid metabolism in epididymal adipose tissue was determined by reverse transcription-quantitative PCR (RT-qPCR).Results:Semaglutide significantly improved systemic metabolism in mice with T2DM, as demonstrated by reductions in body weight, blood glucose, serum lipid levels, and insulin resistance indices homeostasis model assessment of insulin resistance (HOMA-IR) and adipose tissue insulin resistance index (Adipo-IR). Serum Leptin, interleukin-6 (IL-6), and tumor necrosis factor alpha (TNF-\u03b1) levels were downregulated, while Adiponectin levels were elevated. Histological analysis revealed that semaglutide effectively reduced adipocyte size, suppressed macrophage infiltration in adipose tissue, and decreased liver lipid accumulation. Targeted lipidomic profiling identified 24 lipid subclasses, of which 50 lipid molecules were significantly changed after semaglutide treatment. Enrichment analysis identified 15 metabolic pathways, with glycerophospholipid metabolism being the most prominently affected. RT-qPCR results confirmed that semaglutide altered the expression of key genes involved in glycerolipid, glycerophospholipid, fatty acid, and cholesterol metabolism.Conclusions:These results shed light on the comprehensive remodeling of semaglutide in improving lipid metabolism in epididymal white adipose tissue mice with T2DM.<\/jats:p>","DOI":"10.31083\/fbl49873","type":"journal-article","created":{"date-parts":[[2026,7,7]],"date-time":"2026-07-07T10:50:51Z","timestamp":1783421451000},"source":"Crossref","is-referenced-by-count":0,"title":["Semaglutide Modulates Visceral Adipose Tissue Lipid Metabolism in Type 2 Diabetic Mice: A Lipidomics Study"],"prefix":"10.31083","volume":"31","author":[{"ORCID":"https:\/\/orcid.org\/0009-0003-2054-1840","authenticated-orcid":true,"given":"Xinlei","family":"Chen","sequence":"first","affiliation":[{"name":"Department of Endocrinology and Metabolism, Second Affiliated Hospital of Harbin Medical University, 150000 Harbin, Heilongjiang, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0003-9856-4305","authenticated-orcid":true,"given":"Bingrou","family":"Tu","sequence":"additional","affiliation":[{"name":"Department of Endocrinology and Metabolism, Second Affiliated Hospital of Harbin Medical University, 150000 Harbin, Heilongjiang, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0000-0006-8951","authenticated-orcid":true,"given":"Zhaoyuan","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Endocrinology and Metabolism, Second Affiliated Hospital of Harbin Medical University, 150000 Harbin, Heilongjiang, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0005-4111-5829","authenticated-orcid":true,"given":"Ping","family":"Gao","sequence":"additional","affiliation":[{"name":"Department of Endocrinology and Metabolism, Second Affiliated Hospital of Harbin Medical University, 150000 Harbin, Heilongjiang, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2720-0005","authenticated-orcid":true,"given":"Yi","family":"Xu","sequence":"additional","affiliation":[{"name":"Department of Pathology, School of Clinical Medicine, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong, China"},{"name":"Department of Hepatopancreatobiliary Surgery, Second Affiliated Hospital of Harbin Medical University, 150000 Harbin, Heilongjiang, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8567-9101","authenticated-orcid":true,"given":"Yue","family":"Yao","sequence":"additional","affiliation":[{"name":"Department of Endocrinology and Metabolism, Second Affiliated Hospital of Harbin Medical University, 150000 Harbin, Heilongjiang, China"},{"name":"Department of Pathology, School of Clinical Medicine, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"16242","published-online":{"date-parts":[[2026,6,22]]},"reference":[{"key":"ref1","unstructured":"World Obesity Federation. World Obesity Atlas 2025. 2025. Available at: https:\/\/data.worldobesity.org\/publications\/?cat=23 (Accessed: 13 November 2025)."},{"key":"ref2","doi-asserted-by":"publisher","unstructured":"Jayedi A, Soltani S, Motlagh SZT, Emadi A, Shahinfar H, Moosavi H, et al. Anthropometric and adiposity indicators and risk of type 2 diabetes: systematic review and dose-response meta-analysis of cohort studies. BMJ (Clinical Research Ed.). 2022; 376: e067516.","DOI":"10.1136\/bmj-2021-067516"},{"key":"ref3","doi-asserted-by":"publisher","unstructured":"Chait A, den Hartigh LJ. Adipose Tissue Distribution, Inflammation and Its Metabolic Consequences, Including Diabetes and Cardiovascular Disease. Frontiers in Cardiovascular Medicine. 2020; 7: 22.","DOI":"10.3389\/fcvm.2020.00022"},{"key":"ref4","doi-asserted-by":"publisher","unstructured":"Lyu K, Zhang D, Song J, Li X, Perry RJ, Samuel VT, et al. Short-term overnutrition induces white adipose tissue insulin resistance through sn-1,2-diacylglycerol\/PKC\u03b5\/insulin receptor Thr1160 phosphorylation. JCI Insight. 2021; 6: e139946.","DOI":"10.1172\/jci.insight.139946"},{"key":"ref5","doi-asserted-by":"publisher","unstructured":"Tuncman G, Hirosumi J, Solinas G, Chang L, Karin M, Hotamisligil GS. Functional in vivo interactions between JNK1 and JNK2 isoforms in obesity and insulin resistance. Proceedings of the National Academy of Sciences of the United States of America. 2006; 103: 10741\u201310746.","DOI":"10.1073\/pnas.0603509103"},{"key":"ref6","doi-asserted-by":"publisher","unstructured":"American Diabetes Association Professional Practice Committee for Diabetes. 9. Pharmacologic Approaches to Glycemic Treatment: Standards of Care in Diabetes-2026. Diabetes Care. 2026; 49: S183\u2013S215.","DOI":"10.2337\/dc26-S009"},{"key":"ref7","doi-asserted-by":"publisher","unstructured":"Bertoccini L, Baroni MG. GLP-1 Receptor Agonists and SGLT2 Inhibitors for the Treatment of Type 2 Diabetes: New Insights and Opportunities for Cardiovascular Protection. Advances in Experimental Medicine and Biology. 2021; 1307: 193\u2013212.","DOI":"10.1007\/5584_2020_494"},{"key":"ref8","doi-asserted-by":"publisher","unstructured":"Joseph J. The Impact of Semaglutide on Metabolic Syndrome: A Case Report. Cureus. 2025; 17: e87223.","DOI":"10.7759\/cureus.87223"},{"key":"ref9","doi-asserted-by":"publisher","unstructured":"Gao X, Sun H, Wei Y, Niu J, Hao S, Sun H, et al. Protective effect of melatonin against metabolic disorders and neuropsychiatric injuries in type 2 diabetes mellitus mice. Phytomedicine : International Journal of Phytotherapy and Phytopharmacology. 2024; 131: 155805.","DOI":"10.1016\/j.phymed.2024.155805"},{"key":"ref10","doi-asserted-by":"publisher","unstructured":"Zhang K, Pan H, Wang L, Yang H, Zhu H, Gong F. Adipose Tissue Insulin Resistance is Closely Associated with Metabolic Syndrome in Northern Chinese Populations. Diabetes, Metabolic Syndrome and Obesity : Targets and Therapy. 2021; 14: 1117\u20131128.","DOI":"10.2147\/DMSO.S291350"},{"key":"ref11","doi-asserted-by":"publisher","unstructured":"Semnani-Azad Z, Connelly PW, Bazinet RP, Retnakaran R, Jenkins DJA, Harris SB, et al. Adipose Tissue Insulin Resistance Is Longitudinally Associated With Adipose Tissue Dysfunction, Circulating Lipids, and Dysglycemia: The PROMISE Cohort. Diabetes Care. 2021; 44: 1682\u20131691.","DOI":"10.2337\/dc20-1918"},{"key":"ref12","doi-asserted-by":"publisher","unstructured":"Jiang S, Li H, Zhang L, Mu W, Zhang Y, Chen T, et al. Generic Diagramming Platform (GDP): a comprehensive database of high-quality biomedical graphics. Nucleic Acids Research. 2025; 53: D1670\u2013D1676.","DOI":"10.1093\/nar\/gkae973"},{"key":"ref13","doi-asserted-by":"publisher","unstructured":"Ahmad E, Lim S, Lamptey R, Webb DR, Davies MJ. Type 2 diabetes. Lancet (London, England). 2022; 400: 1803\u20131820.","DOI":"10.1016\/S0140-6736(22)01655-5"},{"key":"ref14","doi-asserted-by":"publisher","unstructured":"M\u0142ynarska E, Czarnik W, Dzie\u017ca N, J\u0119draszak W, Majchrowicz G, Prusinowski F, et al. Type 2 Diabetes Mellitus: New Pathogenetic Mechanisms, Treatment and the Most Important Complications. International Journal of Molecular Sciences. 2025; 26: 1094.","DOI":"10.3390\/ijms26031094"},{"key":"ref15","doi-asserted-by":"publisher","unstructured":"Xie C, Yuan Y, Wang Y, Qi C, Wang W, An C, et al. Beyond Discrete Diagnoses: Conceptualizing Obesity-associated Metabolic Disorders as a Unified, Dynamic Continuum. Current Obesity Reports. 2025; 14: 81.","DOI":"10.1007\/s13679-025-00673-5"},{"key":"ref16","doi-asserted-by":"publisher","unstructured":"Rodbard HW, Lingvay I, Reed J, de la Rosa R, Rose L, Sugimoto D, et al. Semaglutide Added to Basal Insulin in Type 2 Diabetes (SUSTAIN 5): A Randomized, Controlled Trial. The Journal of Clinical Endocrinology and Metabolism. 2018; 103: 2291\u20132301.","DOI":"10.1210\/jc.2018-00070"},{"key":"ref17","doi-asserted-by":"publisher","unstructured":"Cantini G, Mannucci E, Luconi M. Perspectives in GLP-1 Research: New Targets, New Receptors. Trends in Endocrinology and Metabolism: TEM. 2016; 27: 427\u2013438.","DOI":"10.1016\/j.tem.2016.03.017"},{"key":"ref18","doi-asserted-by":"publisher","unstructured":"Rodr\u00edguez Jim\u00e9nez B, Rodr\u00edguez de Vera G\u00f3mez P, Belmonte Lomas S, Mesa D\u00edaz \u00c1M, Caballero Mateos I, Gal\u00e1n I, et al. Transforming body composition with semaglutide in adults with obesity and type 2 diabetes mellitus. Frontiers in Endocrinology. 2024; 15: 1386542.","DOI":"10.3389\/fendo.2024.1386542"},{"key":"ref19","doi-asserted-by":"publisher","unstructured":"Li J, Hou H, Zhang Y, Li J. Multimorbidity patterns and their associated factors among patients with type 2 diabetes in China: A hospital-based observational study. Heliyon. 2025; 11: e42905.","DOI":"10.1016\/j.heliyon.2025.e42905"},{"key":"ref20","doi-asserted-by":"publisher","unstructured":"Tiwaskar M, Hwu CM, Lim M, Bhandary A, Chang I. Treatment Preferences for Novel Type 2 Diabetes Oral Medications: Insights from the Asian Diabetes Patient Preference Study. Diabetes Therapy: Research, Treatment and Education of Diabetes and Related Disorders. 2025; 16: 1841\u20131859.","DOI":"10.1007\/s13300-025-01770-3"},{"key":"ref21","doi-asserted-by":"publisher","unstructured":"Wong ND, Sattar N. Cardiovascular risk in diabetes mellitus: epidemiology, assessment and prevention. Nature Reviews. Cardiology. 2023; 20: 685\u2013695.","DOI":"10.1038\/s41569-023-00877-z"},{"key":"ref22","doi-asserted-by":"publisher","unstructured":"Di Folco U, Vallecorsa N, Nardone MR, Pantano AL, Tubili C. Effects of semaglutide on cardiovascular risk factors and eating behaviors in type 2 diabetes. Acta Diabetologica. 2022; 59: 1287\u20131294.","DOI":"10.1007\/s00592-022-01936-6"},{"key":"ref23","doi-asserted-by":"publisher","unstructured":"Gabery S, Salinas CG, Paulsen SJ, Ahnfelt-R\u00f8nne J, Alanentalo T, Baquero AF, et al. Semaglutide lowers body weight in rodents via distributed neural pathways. JCI Insight. 2020; 5: e133429.","DOI":"10.1172\/jci.insight.133429"},{"key":"ref24","doi-asserted-by":"publisher","unstructured":"Wong ND, Karthikeyan H, Fan W. US Population Eligibility and Estimated Impact of Semaglutide Treatment on Obesity Prevalence and Cardiovascular Disease Events. Cardiovascular Drugs and Therapy. 2025; 39: 75\u201384.","DOI":"10.1007\/s10557-023-07488-3"},{"key":"ref25","doi-asserted-by":"publisher","unstructured":"Bays H, Mandarino L, DeFronzo RA. Role of the adipocyte, free fatty acids, and ectopic fat in pathogenesis of type 2 diabetes mellitus: peroxisomal proliferator-activated receptor agonists provide a rational therapeutic approach. The Journal of Clinical Endocrinology and Metabolism. 2004; 89: 463\u2013478.","DOI":"10.1210\/jc.2003-030723"},{"key":"ref26","doi-asserted-by":"publisher","unstructured":"Diraison F, Beylot M. Role of human liver lipogenesis and reesterification in triglycerides secretion and in FFA reesterification. The American Journal of Physiology. 1998; 274: E321\u20137.","DOI":"10.1152\/ajpendo.1998.274.2.E321"},{"key":"ref27","doi-asserted-by":"publisher","unstructured":"McLaughlin T, Lamendola C, Liu A, Abbasi F. Preferential fat deposition in subcutaneous versus visceral depots is associated with insulin sensitivity. The Journal of Clinical Endocrinology and Metabolism. 2011; 96: E1756\u201360.","DOI":"10.1210\/jc.2011-0615"},{"key":"ref28","doi-asserted-by":"publisher","unstructured":"Lomonaco R, Ortiz-Lopez C, Orsak B, Webb A, Hardies J, Darland C, et al. Effect of adipose tissue insulin resistance on metabolic parameters and liver histology in obese patients with nonalcoholic fatty liver disease. Hepatology (Baltimore, Md.). 2012; 55: 1389\u20131397.","DOI":"10.1002\/hep.25539"},{"key":"ref29","doi-asserted-by":"publisher","unstructured":"Teixidor-Deulofeu J, Blid Sk\u00f6ldheden S, Font-Giron\u00e8s F, Feje\u0161 A, Ruud J, Engstr\u00f6m Ruud L. Semaglutide effects on energy balance are mediated by Adcyap1+ neurons in the dorsal vagal complex. Cell Metabolism. 2025; 37: 1530\u20131546.e6.","DOI":"10.1016\/j.cmet.2025.04.018"},{"key":"ref30","doi-asserted-by":"publisher","unstructured":"Byun S, Sotzen MR, Knappenberger MA, Bento MT, Asker M, Olekanma DI, et al. Advantage of Semaglutide: Comprehensive Analysis of Metabolic Impact of Semaglutide-Treated and Pair-Fed Rats. Comprehensive Physiology. 2025; 15: e70083.","DOI":"10.1002\/cph4.70083"},{"key":"ref31","doi-asserted-by":"publisher","unstructured":"Yang J, Ren J, Song J, Liu F, Wu C, Wang X, et al. Glucagon-like peptide 1 regulates adipogenesis in 3T3-L1 preadipocytes. International Journal of Molecular Medicine. 2013; 31: 1429\u20131435.","DOI":"10.3892\/ijmm.2013.1350"},{"key":"ref32","doi-asserted-by":"publisher","unstructured":"Yan K. Recent advances in the effect of adipose tissue inflammation on insulin resistance. Cellular Signalling. 2024; 120: 111229.","DOI":"10.1016\/j.cellsig.2024.111229"},{"key":"ref33","doi-asserted-by":"publisher","unstructured":"Jiang YN, Gao Y, Zhang YS, Min CY, Shen LT, Yan WF, et al. Aggravating effect of abnormal low-density protein cholesterol level on coronary atherosclerotic plaque in type 2 diabetes mellitus patients assessed by coronary computed tomography angiography. Cardiovascular Diabetology. 2024; 23: 234.","DOI":"10.1186\/s12933-024-02304-0"},{"key":"ref34","doi-asserted-by":"publisher","unstructured":"O'Rourke RW, White AE, Metcalf MD, Olivas AS, Mitra P, Larison WG, et al. Hypoxia-induced inflammatory cytokine secretion in human adipose tissue stromovascular cells. Diabetologia. 2011; 54: 1480\u20131490.","DOI":"10.1007\/s00125-011-2103-y"},{"key":"ref35","doi-asserted-by":"publisher","unstructured":"Todosenko N, Yurova K, Khaziakhmatova O, Vulf M, Malashchenko V, Komar A, et al. The Role of (Nuclear) Lipid Droplets in the Pathogenesis of Metabolic Syndrome. Frontiers in Bioscience (Landmark Edition). 2025; 30: 26742.","DOI":"10.31083\/FBL26742"},{"key":"ref36","doi-asserted-by":"publisher","unstructured":"Bendotti G, Montefusco L, Lunati ME, Usuelli V, Pastore I, Lazzaroni E, et al. The anti-inflammatory and immunological properties of GLP-1 Receptor Agonists. Pharmacological Research. 2022; 182: 106320.","DOI":"10.1016\/j.phrs.2022.106320"},{"key":"ref37","doi-asserted-by":"publisher","unstructured":"Miranda AMA, McAllan L, Mazzei G, Andrew I, Davies I, Ertugrul M, et al. Selective remodelling of the adipose niche in obesity and weight loss. Nature. 2025; 644: 769\u2013779.","DOI":"10.1038\/s41586-025-09233-2"},{"key":"ref38","doi-asserted-by":"publisher","unstructured":"Drucker DJ. Mechanisms of Action and Therapeutic Application of Glucagon-like Peptide-1. Cell Metabolism. 2018; 27: 740\u2013756.","DOI":"10.1016\/j.cmet.2018.03.001"},{"key":"ref39","doi-asserted-by":"publisher","unstructured":"Barbarroja N, Lopez-Pedrera C, Garrido-Sanchez L, Mayas MD, Oliva-Olivera W, Bernal-Lopez MR, et al. Progression from high insulin resistance to type 2 diabetes does not entail additional visceral adipose tissue inflammation. PloS One. 2012; 7: e48155.","DOI":"10.1371\/journal.pone.0048155"},{"key":"ref40","doi-asserted-by":"publisher","unstructured":"Lee YS, Park MS, Choung JS, Kim SS, Oh HH, Choi CS, et al. Glucagon-like peptide-1 inhibits adipose tissue macrophage infiltration and inflammation in an obese mouse model of diabetes. Diabetologia. 2012; 55: 2456\u20132468.","DOI":"10.1007\/s00125-012-2592-3"},{"key":"ref41","doi-asserted-by":"publisher","unstructured":"Guo C, Huang T, Chen A, Chen X, Wang L, Shen F, et al. Glucagon-like peptide 1 improves insulin resistance in vitro through anti-inflammation of macrophages. Brazilian Journal of Medical and Biological Research = Revista Brasileira De Pesquisas Medicas E Biologicas. 2016; 49: e5826.","DOI":"10.1590\/1414-431X20165826"},{"key":"ref42","doi-asserted-by":"publisher","unstructured":"Montserrat-de la Paz S, P\u00e9rez-P\u00e9rez A, Vilari\u00f1o-Garc\u00eda T, Jim\u00e9nez-Cortegana C, Muriana FJG, Mill\u00e1n-Linares MC, et al. Nutritional modulation of leptin expression and leptin action in obesity and obesity-associated complications. The Journal of Nutritional Biochemistry. 2021; 89: 108561.","DOI":"10.1016\/j.jnutbio.2020.108561"},{"key":"ref43","doi-asserted-by":"publisher","unstructured":"Tilg H, Ianiro G, Gasbarrini A, Adolph TE. Adipokines: masterminds of metabolic inflammation. Nature Reviews. Immunology. 2025; 25: 250\u2013265.","DOI":"10.1038\/s41577-024-01103-8"},{"key":"ref44","doi-asserted-by":"publisher","unstructured":"Huang CX, Siwan E, Baker CJ, Wei Z, Shinko D, McGuire HM, et al. Uncovering Sex-Related Differences in Skin Macrophage Polarization During Wound Healing in Diabetic Mice. Frontiers in Bioscience (Landmark Edition). 2025; 30: 27113.","DOI":"10.31083\/FBL27113"},{"key":"ref45","doi-asserted-by":"publisher","unstructured":"Gemmink A, Daemen S, Brouwers B, Hoeks J, Schaart G, Knoops K, et al. Decoration of myocellular lipid droplets with perilipins as a marker for in vivo lipid droplet dynamics: A super-resolution microscopy study in trained athletes and insulin resistant individuals. Biochimica et Biophysica Acta. Molecular and Cell Biology of Lipids. 2021; 1866: 158852.","DOI":"10.1016\/j.bbalip.2020.158852"},{"key":"ref46","doi-asserted-by":"publisher","unstructured":"Long C, Li Z, Jiang L, Yang X, Deng S, Jiang Y, et al. Lipid droplet dynamics in type 2 diabetes and its complications: pathophysiological insights and therapeutic options. Lipids in Health and Disease. 2025; 24: 284.","DOI":"10.1186\/s12944-025-02747-8"},{"key":"ref47","doi-asserted-by":"publisher","unstructured":"Herrera-Marcos LV, Mart\u00ednez-Beamonte R, Arnal C, Barranquero C, Puente-Lanzarote JJ, Herrero-Continente T, et al. Dietary squalene supplementation decreases triglyceride species and modifies phospholipid lipidomic profile in the liver of a porcine model of non-alcoholic steatohepatitis. The Journal of Nutritional Biochemistry. 2023; 112: 109207.","DOI":"10.1016\/j.jnutbio.2022.109207"},{"key":"ref48","doi-asserted-by":"publisher","unstructured":"Zhou M, Liu X, Wu Y, Xiang Q, Yu R. Liver Lipidomics Analysis Revealed the Protective mechanism of Zuogui Jiangtang Qinggan Formula in type 2 diabetes mellitus with non-alcoholic fatty liver disease. Journal of Ethnopharmacology. 2024; 329: 118160.","DOI":"10.1016\/j.jep.2024.118160"},{"key":"ref49","doi-asserted-by":"publisher","unstructured":"Pei Y, Song Y, Wang B, Lin C, Yang Y, Li H, et al. Integrated lipidomics and RNA sequencing analysis reveal novel changes during 3T3-L1 cell adipogenesis. PeerJ. 2022; 10: e13417.","DOI":"10.7717\/peerj.13417"},{"key":"ref50","doi-asserted-by":"publisher","unstructured":"Sim JA, Kim J, Yang D. Beyond Lipid Signaling: Pleiotropic Effects of Diacylglycerol Kinases in Cellular Signaling. International Journal of Molecular Sciences. 2020; 21: 6861.","DOI":"10.3390\/ijms21186861"},{"key":"ref51","doi-asserted-by":"publisher","unstructured":"Masenga SK, Kabwe LS, Chakulya M, Kirabo A. Mechanisms of Oxidative Stress in Metabolic Syndrome. International Journal of Molecular Sciences. 2023; 24: 7898.","DOI":"10.3390\/ijms24097898"},{"key":"ref52","doi-asserted-by":"publisher","unstructured":"Szendroedi J, Yoshimura T, Phielix E, Koliaki C, Marcucci M, Zhang D, et al. Role of diacylglycerol activation of PKC\u03b8 in lipid-induced muscle insulin resistance in humans. Proceedings of the National Academy of Sciences of the United States of America. 2014; 111: 9597\u20139602.","DOI":"10.1073\/pnas.1409229111"},{"key":"ref53","doi-asserted-by":"publisher","unstructured":"van der Veen JN, Lingrell S, McCloskey N, LeBlond ND, Galleguillos D, Zhao YY, et al. A role for phosphatidylcholine and phosphatidylethanolamine in hepatic insulin signaling. FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology. 2019; 33: 5045\u20135057.","DOI":"10.1096\/fj.201802117R"},{"key":"ref54","doi-asserted-by":"publisher","unstructured":"Tian Y, Mehta K, Jellinek MJ, Sun H, Lu W, Shi R, et al. Hepatic Phospholipid Remodeling Modulates Insulin Sensitivity and Systemic Metabolism. Advanced Science (Weinheim, Baden-Wurttemberg, Germany). 2023; 10: e2300416.","DOI":"10.1002\/advs.202300416"},{"key":"ref55","doi-asserted-by":"publisher","unstructured":"Guo C, Han X, Zhang T, Zhang H, Li X, Zhou X, et al. Lipidomic analyses reveal potential biomarkers for predicting death and heart failure after acute myocardial infarction. Clinica Chimica Acta; International Journal of Clinical Chemistry. 2024; 562: 119892.","DOI":"10.1016\/j.cca.2024.119892"},{"key":"ref56","doi-asserted-by":"publisher","unstructured":"Kayser BD, Lhomme M, Prifti E, Da Cunha C, Marquet F, Chain F, et al. Phosphatidylglycerols are induced by gut dysbiosis and inflammation, and favorably modulate adipose tissue remodeling in obesity. FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology. 2019; 33: 4741\u20134754.","DOI":"10.1096\/fj.201801897R"},{"key":"ref57","doi-asserted-by":"publisher","unstructured":"Patel V, Joharapurkar A, Kshirsagar S, Sutariya B, Patel M, Patel H, et al. Central administration of coagonist of GLP-1 and glucagon receptors improves dyslipidemia. Biomedicine & Pharmacotherapy = Biomedecine & Pharmacotherapie. 2018; 98: 364\u2013371.","DOI":"10.1016\/j.biopha.2017.12.068"},{"key":"ref58","doi-asserted-by":"publisher","unstructured":"Butovich IA. Cholesteryl esters as a depot for very long chain fatty acids in human meibum. Journal of Lipid Research. 2009; 50: 501\u2013513.","DOI":"10.1194\/jlr.M800426-JLR200"},{"key":"ref59","doi-asserted-by":"publisher","unstructured":"Kawaguchi T, Itou M, Taniguchi E, Sata M. Exendin-4, a glucagon-like peptide-1 receptor agonist, modulates hepatic fatty acid composition and \u0394-5-desaturase index in a murine model of non-alcoholic steatohepatitis. International Journal of Molecular Medicine. 2014; 34: 782\u2013787.","DOI":"10.3892\/ijmm.2014.1826"},{"key":"ref60","doi-asserted-by":"publisher","unstructured":"Yan W, Cui X, Guo T, Liu N, Wang Z, Sun Y, et al. ALOX15 Aggravates Metabolic Dysfunction-Associated Steatotic Liver Disease in Mice with Type 2 Diabetes via Activating the PPAR\u03b3\/CD36 Axis. Antioxidants & Redox Signaling. 2025; 43: 37\u201355.","DOI":"10.1089\/ars.2024.0670"},{"key":"ref61","doi-asserted-by":"publisher","unstructured":"Xu F, Lin B, Zheng X, Chen Z, Cao H, Xu H, et al. GLP-1 receptor agonist promotes brown remodelling in mouse white adipose tissue through SIRT1. Diabetologia. 2016; 59: 1059\u20131069.","DOI":"10.1007\/s00125-016-3896-5"},{"key":"ref62","doi-asserted-by":"publisher","unstructured":"Zhou J, Poudel A, Chandramani-Shivalingappa P, Xu B, Welchko R, Li L. Liraglutide induces beige fat development and promotes mitochondrial function in diet induced obesity mice partially through AMPK-SIRT-1-PGC1-\u03b1 cell signaling pathway. Endocrine. 2019; 64: 271\u2013283.","DOI":"10.1007\/s12020-018-1826-7"},{"key":"ref63","doi-asserted-by":"publisher","unstructured":"Zhao L, Zhu C, Lu M, Chen C, Nie X, Abudukerimu B, et al. The key role of a glucagon-like peptide-1 receptor agonist in body fat redistribution. The Journal of Endocrinology. 2019; 240: 271\u2013286.","DOI":"10.1530\/JOE-18-0374"},{"key":"ref64","doi-asserted-by":"publisher","unstructured":"Sun L, Shang B, Lv S, Liu G, Wu Q, Geng Y. Effects of semaglutide on metabolism and gut microbiota in high-fat diet-induced obese mice. Frontiers in Pharmacology. 2025; 16: 1562896.","DOI":"10.3389\/fphar.2025.1562896"}],"container-title":["Frontiers in Bioscience-Landmark"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.imrpress.com\/journal\/FBL\/31\/6\/10.31083\/FBL49873","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,7,7]],"date-time":"2026-07-07T10:53:27Z","timestamp":1783421607000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.imrpress.com\/journal\/FBL\/31\/6\/10.31083\/FBL49873"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,6,22]]},"references-count":64,"journal-issue":{"issue":"6","published-print":{"date-parts":[[2026]]}},"alternative-id":["S2768-6701(26)02100-3"],"URL":"https:\/\/doi.org\/10.31083\/fbl49873","relation":{},"ISSN":["2768-6701","2768-6698"],"issn-type":[{"value":"2768-6701","type":"print"},{"value":"2768-6698","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,6,22]]},"article-number":"49873"}}