{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,3]],"date-time":"2026-07-03T18:02:48Z","timestamp":1783101768582,"version":"3.54.6"},"reference-count":63,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2025,12,29]],"date-time":"2025-12-29T00:00:00Z","timestamp":1766966400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0"},{"start":{"date-parts":[[2025,12,29]],"date-time":"2025-12-29T00:00:00Z","timestamp":1766966400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0"}],"funder":[{"name":"Science and Technology Innovation Project of the Beijing University of Chinese Medicine","award":["DZMKJCX-2022\u2013004"],"award-info":[{"award-number":["DZMKJCX-2022\u2013004"]}]},{"name":"National Key Research and Development Program \u2018Traditional Chinese Medicine Modernization Research\u2019 Key Special Project","award":["2019YFC1710101"],"award-info":[{"award-number":["2019YFC1710101"]}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Sci Rep"],"DOI":"10.1038\/s41598-025-28985-5","type":"journal-article","created":{"date-parts":[[2025,12,29]],"date-time":"2025-12-29T16:23:08Z","timestamp":1767025388000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Pathogenesis of impaired glucose tolerance in rats based on transcriptome analysis"],"prefix":"10.1038","volume":"15","author":[{"given":"Ran","family":"Yi","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yu","family":"Xie","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yue","family":"Fan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xinyi","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zixuan","family":"Yang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shangjian","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2025,12,29]]},"reference":[{"key":"28985_CR1","doi-asserted-by":"publisher","unstructured":"Global, regional, and national burden of diabetes from 1990 to 2021, with projections of prevalence to 2050: a systematic analysis for the global burden of disease study 2021. Lancet 402, 203\u2013234. https:\/\/doi.org\/10.1016\/s0140-6736(23)01301-6 (2023).","DOI":"10.1016\/s0140-6736(23)01301-6"},{"key":"28985_CR2","doi-asserted-by":"publisher","first-page":"1388","DOI":"10.2337\/dc22-2376","volume":"46","author":"MR Rooney","year":"2023","unstructured":"Rooney, M. R. et al. Global prevalence of prediabetes. Diabetes Care. 46, 1388\u20131394. https:\/\/doi.org\/10.2337\/dc22-2376 (2023).","journal-title":"Diabetes Care"},{"key":"28985_CR3","doi-asserted-by":"publisher","unstructured":"Richter, B., Hemmingsen, B., Metzendorf, M. I. & Takwoingi, Y. Development of type 2 diabetes mellitus in people with intermediate hyperglycaemia. Cochrane Database Syst. Rev. 10, Cd012661. https:\/\/doi.org\/10.1002\/14651858.CD012661.pub2 (2018).","DOI":"10.1002\/14651858.CD012661.pub2"},{"key":"28985_CR4","doi-asserted-by":"publisher","first-page":"1551","DOI":"10.4239\/wjd.v14.i10.1551","volume":"14","author":"YY Li","year":"2023","unstructured":"Li, Y. Y. et al. Analysis of influencing factors and interaction of body weight and disease outcome in patients with prediabetes. World J. Diabetes. 14, 1551\u20131561. https:\/\/doi.org\/10.4239\/wjd.v14.i10.1551 (2023).","journal-title":"World J. Diabetes"},{"key":"28985_CR5","doi-asserted-by":"publisher","unstructured":"Luc, K., Schramm-Luc, A., Guzik, T. J. & Mikolajczyk, T. P. Oxidative stress and inflammatory markers in prediabetes and diabetes. J. Physiol. Pharmacol. 70 https:\/\/doi.org\/10.26402\/jpp.2019.6.01 (2019).","DOI":"10.26402\/jpp.2019.6.01"},{"key":"28985_CR6","doi-asserted-by":"publisher","first-page":"2279","DOI":"10.1016\/s0140-6736(12)60283-9","volume":"379","author":"AG Tab\u00e1k","year":"2012","unstructured":"Tab\u00e1k, A. G., Herder, C., Rathmann, W., Brunner, E. J. & Kivim\u00e4ki, M. Prediabetes: a high-risk state for diabetes development. Lancet 379, 2279\u20132290. https:\/\/doi.org\/10.1016\/s0140-6736(12)60283-9 (2012).","journal-title":"Lancet"},{"key":"28985_CR7","doi-asserted-by":"publisher","first-page":"393","DOI":"10.1056\/NEJMoa012512","volume":"346","author":"WC Knowler","year":"2002","unstructured":"Knowler, W. C. et al. Reduction in the incidence of type 2 diabetes with lifestyle intervention or metformin. N Engl. J. Med. 346, 393\u2013403. https:\/\/doi.org\/10.1056\/NEJMoa012512 (2002).","journal-title":"N Engl. J. Med."},{"key":"28985_CR8","doi-asserted-by":"publisher","first-page":"296","DOI":"10.1007\/s12020-020-02226-3","volume":"68","author":"P Zhang","year":"2020","unstructured":"Zhang, P. et al. Screening and functional studies of long noncoding RNA in subjects with prediabetes. Endocrine 68, 296\u2013305. https:\/\/doi.org\/10.1007\/s12020-020-02226-3 (2020).","journal-title":"Endocrine"},{"key":"28985_CR9","doi-asserted-by":"publisher","first-page":"756","DOI":"10.1016\/j.jaci.2022.08.016","volume":"150","author":"CM Moore","year":"2022","unstructured":"Moore, C. M. & Seibold, M. A. Possibilities and promise: leveraging advances in transcriptomics for clinical decision making in allergic diseases. J. Allergy Clin. Immunol. 150, 756\u2013765. https:\/\/doi.org\/10.1016\/j.jaci.2022.08.016 (2022).","journal-title":"J. Allergy Clin. Immunol."},{"key":"28985_CR10","doi-asserted-by":"publisher","first-page":"9237","DOI":"10.12659\/msm.918407","volume":"25","author":"X Che","year":"2019","unstructured":"Che, X. et al. Differently expressed genes (DEGs) relevant to type 2 diabetes mellitus identification and pathway analysis via integrated bioinformatics analysis. Med. Sci. Monit. 25, 9237\u20139244. https:\/\/doi.org\/10.12659\/msm.918407 (2019).","journal-title":"Med. Sci. Monit."},{"key":"28985_CR11","doi-asserted-by":"publisher","first-page":"e13932","DOI":"10.7717\/peerj.13932","volume":"10","author":"J Zhao","year":"2022","unstructured":"Zhao, J. et al. Bioinformatics prediction and experimental verification of key biomarkers for diabetic kidney disease based on transcriptome sequencing in mice. PeerJ 10, e13932. https:\/\/doi.org\/10.7717\/peerj.13932 (2022).","journal-title":"PeerJ"},{"key":"28985_CR12","doi-asserted-by":"publisher","first-page":"507","DOI":"10.1152\/physrev.00024.2006","volume":"87","author":"DB Savage","year":"2007","unstructured":"Savage, D. B., Petersen, K. F. & Shulman, G. I. Disordered lipid metabolism and the pathogenesis of insulin resistance. Physiol. Rev. 87, 507\u2013520. https:\/\/doi.org\/10.1152\/physrev.00024.2006 (2007).","journal-title":"Physiol. Rev."},{"key":"28985_CR13","doi-asserted-by":"publisher","first-page":"27","DOI":"10.1093\/nar\/28.1.27","volume":"28","author":"M Kanehisa","year":"2000","unstructured":"Kanehisa, M. & Goto, S. KEGG: Kyoto encyclopedia of genes and genomes. Nucleic Acids Res. 28, 27\u201330. https:\/\/doi.org\/10.1093\/nar\/28.1.27 (2000).","journal-title":"Nucleic Acids Res."},{"key":"28985_CR14","doi-asserted-by":"publisher","first-page":"D457","DOI":"10.1093\/nar\/gkv1070","volume":"44","author":"M Kanehisa","year":"2016","unstructured":"Kanehisa, M., Sato, Y., Kawashima, M., Furumichi, M. & Tanabe, M. KEGG as a reference resource for gene and protein annotation. Nucleic Acids Res. 44, D457\u2013462. https:\/\/doi.org\/10.1093\/nar\/gkv1070 (2016).","journal-title":"Nucleic Acids Res."},{"key":"28985_CR15","doi-asserted-by":"publisher","first-page":"7062","DOI":"10.1074\/jbc.M007894200","volume":"276","author":"KJ Waite","year":"2001","unstructured":"Waite, K. J., Floyd, Z. E., Arbour-Reily, P. & Stephens, J. M. Interferon-gamma-induced regulation of peroxisome proliferator-activated receptor gamma and stats in adipocytes. J. Biol. Chem. 276, 7062\u20137068. https:\/\/doi.org\/10.1074\/jbc.M007894200 (2001).","journal-title":"J. Biol. Chem."},{"key":"28985_CR16","doi-asserted-by":"publisher","first-page":"116557","DOI":"10.1016\/j.jep.2023.116557","volume":"313","author":"HF Zhou","year":"2023","unstructured":"Zhou, H. F. et al. Quercetin serves as the major component of Xiang-lian pill to ameliorate ulcerative colitis via tipping the balance of STAT1\/PPAR\u03b3 and dictating the alternative activation of macrophage. J. Ethnopharmacol. 313, 116557. https:\/\/doi.org\/10.1016\/j.jep.2023.116557 (2023).","journal-title":"J. Ethnopharmacol."},{"key":"28985_CR17","doi-asserted-by":"publisher","first-page":"720","DOI":"10.2337\/db20-0634","volume":"70","author":"A Antony","year":"2021","unstructured":"Antony, A. et al. Deficiency of Stat1 in CD11c(+) cells alters adipose tissue inflammation and improves metabolic dysfunctions in mice fed a high-fat diet. Diabetes 70, 720\u2013732. https:\/\/doi.org\/10.2337\/db20-0634 (2021).","journal-title":"Diabetes"},{"key":"28985_CR18","doi-asserted-by":"publisher","first-page":"1895","DOI":"10.3389\/fimmu.2019.01895","volume":"10","author":"Y Tian","year":"2019","unstructured":"Tian, Y. et al. Procyanidin B2 activates PPAR\u03b3 to induce M2 polarization in mouse macrophages. Front. Immunol. 10, 1895. https:\/\/doi.org\/10.3389\/fimmu.2019.01895 (2019).","journal-title":"Front. Immunol."},{"key":"28985_CR19","doi-asserted-by":"publisher","first-page":"109980","DOI":"10.1016\/j.diabres.2022.109980","volume":"190","author":"JS Neves","year":"2022","unstructured":"Neves, J. S. et al. Management of dyslipidemia and atherosclerotic cardiovascular risk in prediabetes. Diabetes Res. Clin. Pract. 190, 109980. https:\/\/doi.org\/10.1016\/j.diabres.2022.109980 (2022).","journal-title":"Diabetes Res. Clin. Pract."},{"key":"28985_CR20","doi-asserted-by":"publisher","unstructured":"La Sala, L. & Pontiroli, A. E. Prevention of diabetes and cardiovascular disease in obesity. Int. J. Mol. Sci. 21 https:\/\/doi.org\/10.3390\/ijms21218178 (2020).","DOI":"10.3390\/ijms21218178"},{"key":"28985_CR21","doi-asserted-by":"publisher","first-page":"332","DOI":"10.1016\/j.clnu.2023.12.005","volume":"43","author":"Y Li","year":"2024","unstructured":"Li, Y. et al. Peroxisome proliferator-activated receptors: A key link between lipid metabolism and cancer progression. Clin. Nutr. 43, 332\u2013345. https:\/\/doi.org\/10.1016\/j.clnu.2023.12.005 (2024).","journal-title":"Clin. Nutr."},{"key":"28985_CR22","doi-asserted-by":"publisher","first-page":"502","DOI":"10.1016\/j.ejmech.2019.01.067","volume":"166","author":"AZ Mirza","year":"2019","unstructured":"Mirza, A. Z., Althagafi, I. I. & Shamshad, H. Role of PPAR receptor in different diseases and their ligands: physiological importance and clinical implications. Eur. J. Med. Chem. 166, 502\u2013513. https:\/\/doi.org\/10.1016\/j.ejmech.2019.01.067 (2019).","journal-title":"Eur. J. Med. Chem."},{"key":"28985_CR23","doi-asserted-by":"publisher","first-page":"367","DOI":"10.1038\/nrm2391","volume":"9","author":"A Guilherme","year":"2008","unstructured":"Guilherme, A., Virbasius, J. V., Puri, V. & Czech, M. P. Adipocyte dysfunctions linking obesity to insulin resistance and type 2 diabetes. Nat. Rev. Mol. Cell. Biol. 9, 367\u2013377. https:\/\/doi.org\/10.1038\/nrm2391 (2008).","journal-title":"Nat. Rev. Mol. Cell. Biol."},{"key":"28985_CR24","doi-asserted-by":"publisher","first-page":"9","DOI":"10.1016\/j.plefa.2018.11.015","volume":"141","author":"J Labrecque","year":"2019","unstructured":"Labrecque, J. et al. Interleukin-1\u03b2 and prostaglandin-synthesizing enzymes as modulators of human omental and subcutaneous adipose tissue function. Prostaglandins Leukot. Essent. Fat. Acids. 141, 9\u201316. https:\/\/doi.org\/10.1016\/j.plefa.2018.11.015 (2019).","journal-title":"Prostaglandins Leukot. Essent. Fat. Acids"},{"key":"28985_CR25","doi-asserted-by":"publisher","first-page":"16","DOI":"10.1186\/s40246-024-00582-z","volume":"18","author":"MI Farrim","year":"2024","unstructured":"Farrim, M. I., Gomes, A., Milenkovic, D. & Menezes, R. Gene expression analysis reveals diabetes-related gene signatures. Hum. Genomics. 18, 16. https:\/\/doi.org\/10.1186\/s40246-024-00582-z (2024).","journal-title":"Hum. Genomics"},{"key":"28985_CR26","doi-asserted-by":"publisher","first-page":"31936","DOI":"10.1074\/jbc.M109.061655","volume":"284","author":"FC McGillicuddy","year":"2009","unstructured":"McGillicuddy, F. C. et al. Interferon gamma attenuates insulin signaling, lipid storage, and differentiation in human adipocytes via activation of the JAK\/STAT pathway. J. Biol. Chem. 284, 31936\u201331944. https:\/\/doi.org\/10.1074\/jbc.M109.061655 (2009).","journal-title":"J. Biol. Chem."},{"key":"28985_CR27","doi-asserted-by":"publisher","first-page":"431","DOI":"10.1016\/j.bbadis.2013.05.030","volume":"1842","author":"AJ Richard","year":"2014","unstructured":"Richard, A. J. & Stephens, J. M. The role of JAK-STAT signaling in adipose tissue function. Biochim. Biophys. Acta. 1842, 431\u2013439. https:\/\/doi.org\/10.1016\/j.bbadis.2013.05.030 (2014).","journal-title":"Biochim. Biophys. Acta"},{"key":"28985_CR28","doi-asserted-by":"publisher","first-page":"301","DOI":"10.3109\/10408363.2015.1041582","volume":"52","author":"S Laforest","year":"2015","unstructured":"Laforest, S., Labrecque, J., Michaud, A., Cianflone, K. & Tchernof, A. Adipocyte size as a determinant of metabolic disease and adipose tissue dysfunction. Crit. Rev. Clin. Lab. Sci. 52, 301\u2013313. https:\/\/doi.org\/10.3109\/10408363.2015.1041582 (2015).","journal-title":"Crit. Rev. Clin. Lab. Sci."},{"key":"28985_CR29","doi-asserted-by":"publisher","first-page":"154338","DOI":"10.1016\/j.metabol.2020.154338","volume":"114","author":"A Christofides","year":"2021","unstructured":"Christofides, A., Konstantinidou, E., Jani, C. & Boussiotis, V. A. The role of peroxisome proliferator-activated receptors (PPAR) in immune responses. Metabolism 114, 154338. https:\/\/doi.org\/10.1016\/j.metabol.2020.154338 (2021).","journal-title":"Metabolism"},{"key":"28985_CR30","doi-asserted-by":"publisher","unstructured":"Bailey, T., Nieto, A. & McDonald, P. Inhibition of the monocarboxylate transporter 1 (MCT1) promotes 3T3-L1 adipocyte proliferation and enhances insulin sensitivity. Int. J. Mol. Sci. 23 https:\/\/doi.org\/10.3390\/ijms23031901 (2022).","DOI":"10.3390\/ijms23031901"},{"key":"28985_CR31","doi-asserted-by":"publisher","first-page":"14959","DOI":"10.1021\/acs.jafc.2c05549","volume":"70","author":"Y Jing","year":"2022","unstructured":"Jing, Y. et al. Knockout and restoration reveal differential functional roles of PPAR\u03b31 and PPAR\u03b32 in chicken adipogenesis. J. Agric. Food Chem. 70, 14959\u201314973. https:\/\/doi.org\/10.1021\/acs.jafc.2c05549 (2022).","journal-title":"J. Agric. Food Chem."},{"key":"28985_CR32","doi-asserted-by":"publisher","first-page":"1577","DOI":"10.1016\/j.celrep.2018.10.035","volume":"25","author":"M Aprile","year":"2018","unstructured":"Aprile, M. et al. PPAR\u03b3\u22065, a naturally occurring dominant-negative splice isoform, impairs PPAR\u03b3 function and adipocyte differentiation. Cell. Rep. 25, 1577\u20131592.e1576. https:\/\/doi.org\/10.1016\/j.celrep.2018.10.035 (2018).","journal-title":"Cell. Rep."},{"key":"28985_CR33","doi-asserted-by":"publisher","first-page":"e7378","DOI":"10.1097\/md.0000000000007378","volume":"96","author":"X Wang","year":"2017","unstructured":"Wang, X. et al. A cross-sectional study on the associations of insulin resistance with sex hormone, abnormal lipid metabolism in T2DM and IGT patients. Med. (Baltim). 96, e7378. https:\/\/doi.org\/10.1097\/md.0000000000007378 (2017).","journal-title":"Med. (Baltim)."},{"key":"28985_CR34","doi-asserted-by":"publisher","first-page":"219","DOI":"10.1146\/annurev-physiol-021909-135846","volume":"72","author":"JM Olefsky","year":"2010","unstructured":"Olefsky, J. M. & Glass, C. K. Macrophages, inflammation, and insulin resistance. Annu. Rev. Physiol. 72, 219\u2013246. https:\/\/doi.org\/10.1146\/annurev-physiol-021909-135846 (2010).","journal-title":"Annu. Rev. Physiol."},{"key":"28985_CR35","doi-asserted-by":"publisher","first-page":"1121","DOI":"10.1038\/s41374-022-00786-8","volume":"102","author":"J Qiu","year":"2022","unstructured":"Qiu, J., Shu, C., Li, X. & Zhang, W. C. PAQR3 depletion accelerates diabetic wound healing by promoting angiogenesis through inhibiting STUB1-mediated PPAR\u03b3 degradation. Lab. Invest. 102, 1121\u20131131. https:\/\/doi.org\/10.1038\/s41374-022-00786-8 (2022).","journal-title":"Lab. Invest."},{"key":"28985_CR36","doi-asserted-by":"publisher","first-page":"2966","DOI":"10.2337\/db16-0317","volume":"65","author":"F Zhuge","year":"2016","unstructured":"Zhuge, F. et al. DPP-4 Inhibition by linagliptin attenuates obesity-related inflammation and insulin resistance by regulating M1\/M2 macrophage polarization. Diabetes 65, 2966\u20132979. https:\/\/doi.org\/10.2337\/db16-0317 (2016).","journal-title":"Diabetes"},{"key":"28985_CR37","doi-asserted-by":"publisher","first-page":"750","DOI":"10.1038\/nri3088","volume":"11","author":"T Lawrence","year":"2011","unstructured":"Lawrence, T. & Natoli, G. Transcriptional regulation of macrophage polarization: enabling diversity with identity. Nat. Rev. Immunol. 11, 750\u2013761. https:\/\/doi.org\/10.1038\/nri3088 (2011).","journal-title":"Nat. Rev. Immunol."},{"key":"28985_CR38","doi-asserted-by":"publisher","unstructured":"Li, H. et al. Macrophages, chronic inflammation, and insulin resistance. Cells 11 https:\/\/doi.org\/10.3390\/cells11193001 (2022).","DOI":"10.3390\/cells11193001"},{"key":"28985_CR39","doi-asserted-by":"publisher","first-page":"109955","DOI":"10.1016\/j.celrep.2021.109955","volume":"37","author":"L He","year":"2021","unstructured":"He, L. et al. Global characterization of macrophage polarization mechanisms and identification of M2-type polarization inhibitors. Cell. Rep. 37, 109955. https:\/\/doi.org\/10.1016\/j.celrep.2021.109955 (2021).","journal-title":"Cell. Rep."},{"key":"28985_CR40","doi-asserted-by":"publisher","first-page":"346","DOI":"10.2337\/db11-0860","volume":"61","author":"DY Oh","year":"2012","unstructured":"Oh, D. Y., Morinaga, H., Talukdar, S., Bae, E. J. & Olefsky, J. M. Increased macrophage migration into adipose tissue in obese mice. Diabetes 61, 346\u2013354. https:\/\/doi.org\/10.2337\/db11-0860 (2012).","journal-title":"Diabetes"},{"key":"28985_CR41","doi-asserted-by":"publisher","first-page":"429","DOI":"10.1007\/s10517-018-4186-7","volume":"165","author":"YS Stafeev","year":"2018","unstructured":"Stafeev, Y. S. et al. Modulation of the inflammatory status of macrophages and their paracrine effect on the sensitivity of adipocytes to insulin with sirtuin and PPAR\u03b3 receptor activators. Bull. Exp. Biol. Med. 165, 429\u2013433. https:\/\/doi.org\/10.1007\/s10517-018-4186-7 (2018).","journal-title":"Bull. Exp. Biol. Med."},{"key":"28985_CR42","doi-asserted-by":"publisher","first-page":"389","DOI":"10.1530\/eje-08-0201","volume":"159","author":"A Colao","year":"2008","unstructured":"Colao, A. et al. Relationships between serum IGF1 levels, blood pressure, and glucose tolerance: an observational, exploratory study in 404 subjects. Eur. J. Endocrinol. 159, 389\u2013397. https:\/\/doi.org\/10.1530\/eje-08-0201 (2008).","journal-title":"Eur. J. Endocrinol."},{"key":"28985_CR43","doi-asserted-by":"publisher","unstructured":"Homan, E. P. et al. Differential roles of FOXO transcription factors on insulin action in brown and white adipose tissue. J. Clin. Invest. 131 https:\/\/doi.org\/10.1172\/jci143328 (2021).","DOI":"10.1172\/jci143328"},{"key":"28985_CR44","doi-asserted-by":"publisher","first-page":"172","DOI":"10.1002\/oby.21354","volume":"24","author":"HR Chang","year":"2016","unstructured":"Chang, H. R., Kim, H. J., Xu, X. & Ferrante, A. W. Jr. Macrophage and adipocyte IGF1 maintain adipose tissue homeostasis during metabolic stresses. Obes. (Silver Spring). 24, 172\u2013183. https:\/\/doi.org\/10.1002\/oby.21354 (2016).","journal-title":"Obes. (Silver Spring)"},{"key":"28985_CR45","doi-asserted-by":"publisher","first-page":"4976","DOI":"10.1039\/c6fo01261b","volume":"7","author":"O Lv","year":"2016","unstructured":"Lv, O., Wang, L., Li, J., Ma, Q. & Zhao, W. Effects of pomegranate peel polyphenols on lipid accumulation and cholesterol metabolic transformation in L-02 human hepatic cells via the PPAR\u03b3-ABCA1\/CYP7A1 pathway. Food Funct. 7, 4976\u20134983. https:\/\/doi.org\/10.1039\/c6fo01261b (2016).","journal-title":"Food Funct."},{"key":"28985_CR46","doi-asserted-by":"publisher","first-page":"19","DOI":"10.1016\/j.bbalip.2014.04.008","volume":"1851","author":"Y Qi","year":"2015","unstructured":"Qi, Y. et al. Bile acid signaling in lipid metabolism: metabolomic and lipidomic analysis of lipid and bile acid markers linked to anti-obesity and anti-diabetes in mice. Biochim. Biophys. Acta. 1851, 19\u201329. https:\/\/doi.org\/10.1016\/j.bbalip.2014.04.008 (2015).","journal-title":"Biochim. Biophys. Acta"},{"key":"28985_CR47","doi-asserted-by":"publisher","first-page":"1006","DOI":"10.1073\/pnas.0506982103","volume":"103","author":"Y Zhang","year":"2006","unstructured":"Zhang, Y. et al. Activation of the nuclear receptor FXR improves hyperglycemia and hyperlipidemia in diabetic mice. Proc. Natl. Acad. Sci. U S A. 103, 1006\u20131011. https:\/\/doi.org\/10.1073\/pnas.0506982103 (2006).","journal-title":"Proc. Natl. Acad. Sci. U S A"},{"key":"28985_CR48","doi-asserted-by":"publisher","first-page":"1811","DOI":"10.1038\/s41366-021-00850-1","volume":"45","author":"V D\u2019Esposito","year":"2021","unstructured":"D\u2019Esposito, V. et al. In severe obesity, subcutaneous adipose tissue cell-derived cytokines are early markers of impaired glucose tolerance and are modulated by quercetin. Int. J. Obes. (Lond). 45, 1811\u20131820. https:\/\/doi.org\/10.1038\/s41366-021-00850-1 (2021).","journal-title":"Int. J. Obes. (Lond)"},{"key":"28985_CR49","doi-asserted-by":"publisher","first-page":"619","DOI":"10.1080\/08820139.2020.1860085","volume":"51","author":"X Cheng","year":"2022","unstructured":"Cheng, X., Liu, Y., Lin, N., Deng, S. & Wan, Q. Association between Interleukin-1\u03b2 polymorphism at Rs16944 and glucose metabolism: A cohort study. Immunol. Invest. 51, 619\u2013629. https:\/\/doi.org\/10.1080\/08820139.2020.1860085 (2022).","journal-title":"Immunol. Invest."},{"key":"28985_CR50","doi-asserted-by":"publisher","first-page":"82","DOI":"10.3109\/08830185.2014.969421","volume":"34","author":"L Zhu","year":"2015","unstructured":"Zhu, L., Zhao, Q., Yang, T., Ding, W. & Zhao, Y. Cellular metabolism and macrophage functional polarization. Int. Rev. Immunol. 34, 82\u2013100. https:\/\/doi.org\/10.3109\/08830185.2014.969421 (2015).","journal-title":"Int. Rev. Immunol."},{"key":"28985_CR51","doi-asserted-by":"publisher","first-page":"579","DOI":"10.1097\/pai.0000000000000782","volume":"28","author":"MJ Cho","year":"2020","unstructured":"Cho, M. J. et al. MHY2013 modulates age-related inflammation and insulin resistance by suppressing the Akt\/FOXO1\/IL-1\u03b2 axis and MAPK-mediated NF-\u03baB signaling in aged rat liver. Appl. Immunohistochem. Mol. Morphol. 28, 579\u2013592. https:\/\/doi.org\/10.1097\/pai.0000000000000782 (2020).","journal-title":"Appl. Immunohistochem. Mol. Morphol."},{"key":"28985_CR52","first-page":"10","volume":"26","author":"LS Silveira","year":"2020","unstructured":"Silveira, L. S. et al. Macrophage immunophenotype but not anti-inflammatory profile is modulated by peroxisome proliferator-activated receptor gamma (PPAR\u03b3) in exercised obese mice. Exerc. Immunol. Rev. 26, 10\u201322 (2020).","journal-title":"Exerc. Immunol. Rev."},{"key":"28985_CR53","doi-asserted-by":"publisher","unstructured":"Mao, H., Han, B., Li, H., Tao, Y. & Wu, W. FABP4 knockdown suppresses inflammation, apoptosis and extracellular matrix degradation in IL-1\u03b2-induced chondrocytes by activating PPAR\u03b3 to regulate the NF-\u03baB signaling pathway. Mol. Med. Rep. 24 https:\/\/doi.org\/10.3892\/mmr.2021.12495 (2021).","DOI":"10.3892\/mmr.2021.12495"},{"key":"28985_CR54","doi-asserted-by":"publisher","first-page":"1679","DOI":"10.1053\/j.gastro.2017.01.055","volume":"152","author":"O Ch\u00e1vez-Talavera","year":"2017","unstructured":"Ch\u00e1vez-Talavera, O., Tailleux, A., Lefebvre, P. & Staels, B. Bile acid control of metabolism and inflammation in obesity, type 2 diabetes, dyslipidemia, and nonalcoholic fatty liver disease. Gastroenterology 152, 1679\u20131694.e1673. https:\/\/doi.org\/10.1053\/j.gastro.2017.01.055 (2017).","journal-title":"Gastroenterology"},{"key":"28985_CR55","doi-asserted-by":"publisher","first-page":"149","DOI":"10.4161\/21623945.2014.979661","volume":"4","author":"C Bing","year":"2015","unstructured":"Bing, C. Is interleukin-1\u03b2 a culprit in macrophage-adipocyte crosstalk in obesity? Adipocyte 4, 149\u2013152. https:\/\/doi.org\/10.4161\/21623945.2014.979661 (2015).","journal-title":"Adipocyte"},{"key":"28985_CR56","doi-asserted-by":"publisher","first-page":"106572","DOI":"10.1016\/j.isci.2023.106572","volume":"26","author":"Z Shen","year":"2023","unstructured":"Shen, Z. et al. Expansion of macrophage and liver sinusoidal endothelial cell subpopulations during non-alcoholic steatohepatitis progression. iScience 26, 106572. https:\/\/doi.org\/10.1016\/j.isci.2023.106572 (2023).","journal-title":"iScience"},{"key":"28985_CR57","doi-asserted-by":"publisher","first-page":"1172","DOI":"10.3945\/jn.110.127068","volume":"141","author":"AP Thomas","year":"2011","unstructured":"Thomas, A. P., Dunn, T. N., Oort, P. J., Grino, M. & Adams, S. H. Inflammatory phenotyping identifies CD11d as a gene markedly induced in white adipose tissue in obese rodents and women. J. Nutr. 141, 1172\u20131180. https:\/\/doi.org\/10.3945\/jn.110.127068 (2011).","journal-title":"J. Nutr."},{"key":"28985_CR58","doi-asserted-by":"publisher","unstructured":"Zhai, M. et al. Identification of three significant genes associated with immune cells infiltration in dysfunctional adipose tissue-induced insulin-resistance of obese patients via comprehensive bioinformatics analysis. Int. J. Endocrinol. 2021, 8820089. https:\/\/doi.org\/10.1155\/2021\/8820089 (2021).","DOI":"10.1155\/2021\/8820089"},{"key":"28985_CR59","doi-asserted-by":"publisher","first-page":"1128136","DOI":"10.3389\/fgene.2023.1128136","volume":"14","author":"B Li","year":"2023","unstructured":"Li, B., Zhao, X., Xie, W., Hong, Z. & Zhang, Y. Integrative analyses of biomarkers and pathways for diabetic nephropathy. Front. Genet. 14, 1128136. https:\/\/doi.org\/10.3389\/fgene.2023.1128136 (2023).","journal-title":"Front. Genet."},{"key":"28985_CR60","doi-asserted-by":"publisher","first-page":"672","DOI":"10.14202\/vetworld.2022.672-678","volume":"15","author":"DGB Krisnamurti","year":"2022","unstructured":"Krisnamurti, D. G. B., Purwaningsih, E. H., Tarigan, T. J. E., Soetikno, V. & Louisa, M. Hematological indices and their correlation with glucose control parameters in a prediabetic rat model. Vet. World. 15, 672\u2013678. https:\/\/doi.org\/10.14202\/vetworld.2022.672-678 (2022).","journal-title":"Vet. World"},{"key":"28985_CR61","doi-asserted-by":"publisher","first-page":"1547","DOI":"10.1111\/dom.15002","volume":"25","author":"EG Hoffman","year":"2023","unstructured":"Hoffman, E. G. et al. Effects of somatostatin receptor type 2 antagonism during insulin-induced hypoglycaemia in male rats with prediabetes. Diabetes Obes. Metab. 25, 1547\u20131556. https:\/\/doi.org\/10.1111\/dom.15002 (2023).","journal-title":"Diabetes Obes. Metab."},{"key":"28985_CR62","doi-asserted-by":"publisher","first-page":"S1","DOI":"10.2337\/dc24-SINT","volume":"47","author":"Introduction and Methodology","year":"2024","unstructured":"Introduction and Methodology. Standards of care in diabetes-2024. Diabetes Care. 47, S1\u2013s4. https:\/\/doi.org\/10.2337\/dc24-SINT (2024).","journal-title":"Diabetes Care"},{"key":"28985_CR63","doi-asserted-by":"publisher","first-page":"550","DOI":"10.1186\/s13059-014-0550-8","volume":"15","author":"MI Love","year":"2014","unstructured":"Love, M. I., Huber, W. & Anders, S. Moderated estimation of fold change and dispersion for RNA-seq data with DESeq2. Genome Biol. 15, 550. https:\/\/doi.org\/10.1186\/s13059-014-0550-8 (2014).","journal-title":"Genome Biol."}],"container-title":["Scientific Reports"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/s41598-025-28985-5.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41598-025-28985-5","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41598-025-28985-5.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,4,25]],"date-time":"2026-04-25T12:28:31Z","timestamp":1777120111000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/s41598-025-28985-5"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,12,29]]},"references-count":63,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2025,12]]}},"alternative-id":["28985"],"URL":"https:\/\/doi.org\/10.1038\/s41598-025-28985-5","relation":{},"ISSN":["2045-2322"],"issn-type":[{"value":"2045-2322","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,12,29]]},"assertion":[{"value":"27 January 2025","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"13 November 2025","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"29 December 2025","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"The authors declare no competing interests.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"44908"}}