{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,18]],"date-time":"2026-01-18T06:41:05Z","timestamp":1768718465909,"version":"3.49.0"},"reference-count":40,"publisher":"MDPI AG","issue":"20","license":[{"start":{"date-parts":[[2024,10,17]],"date-time":"2024-10-17T00:00:00Z","timestamp":1729123200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Transformation Project of Scientific and Technological Achievements in the Qinghai Province","award":["2020-SF-162"],"award-info":[{"award-number":["2020-SF-162"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Nutrients"],"abstract":"<jats:p>Objectives: Highland barley (HB) consumption offers numerous health benefits; however, its impact on glycolipid metabolism abnormalities induced by a high-fat diet remains unclear. Consequently, this study aimed to investigate the therapeutic effects and underlying molecular mechanisms of HB in the context of obesity; Methods: Rats were fed either a high-fat diet (HFD) to induce obesity or a standard diet (SD) for six weeks. The rats in the HFD group were randomly assigned into five groups: HFD+HFD, HFD+SD, and low (30%), medium (45%), and high (60%) doses of the HB diet for an additional ten weeks. Analyses of serum lipid profiles, liver histology, transcriptomes, and untargeted metabolomes were conducted; Results: HB intake resulted in decreased weight gain, reduced feed intake, lower serum triglyceride and cholesterol levels, and diminished hepatic lipid accumulation. It also improved insulin and fasting blood glucose levels, and antioxidant capacity in the HFD-fed rats. Transcriptome analysis revealed that HB supplementation significantly suppressed the HFD-induced increase in the expression of Angptl8, Apof, CYP7A1, GDF15, Marveld1, and Nr0b2. Furthermore, HB supplementation reversed the HFD-induced decrease in Pex11a expression. Untargeted metabolome analysis indicated that HB primarily influenced the pentose phosphate pathway, the Warburg effect, and tryptophan metabolism. Additionally, integrated transcriptome and metabolome analyses demonstrated that the treatments affected the expression of genes associated with glycolipid metabolism, specifically ABCG8, CYP2C12, CYP2C24, CYP7A1, and IRS2. Western blotting confirmed that HB supplementation impacted the IRS2\/PI3K\/AKT signaling pathway; Conclusions: HB alleviates HFD-induced obesity and liver injury in an obese rat model possibly through the IRS2\/PI3K\/Akt signaling pathway.<\/jats:p>","DOI":"10.3390\/nu16203518","type":"journal-article","created":{"date-parts":[[2024,10,17]],"date-time":"2024-10-17T08:56:32Z","timestamp":1729155392000},"page":"3518","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Highland Barley Alleviates High-Fat Diet-Induced Obesity and Liver Injury Through the IRS2\/PI3K\/AKT Signaling Pathway in Rats"],"prefix":"10.3390","volume":"16","author":[{"given":"Xiaodong","family":"Shi","sequence":"first","affiliation":[{"name":"Beijing Key Laboratory of the Innovative Development of Functional Staple and the Nutritional Intervention for Chronic Disease, Department of Clinical Nutrition, Department of Health Medicine, Peking Union Medical College Hospital, Peking Union Medical College, Chinese Academy of Medical Sciences, Beijing 100730, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wei","family":"Song","sequence":"additional","affiliation":[{"name":"Center for Biomarker Discovery and Validation, Institute of Clinical Medicine, Peking Union Medical College Hospital, Peking Union Medical College, Chinese Academy of Medical Sciences, Beijing 100730, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Boyue","family":"Jiang","sequence":"additional","affiliation":[{"name":"Department of Hepato-Bilio-Pancreatic Surgery, Department of General Surgery, Beijing Hospital, National Center of Gerontology, Institute of Geriatric Medicine, Peking Union Medical College, Chinese Academy of Medical Sciences, Beijing 100730, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jie","family":"Ma","sequence":"additional","affiliation":[{"name":"Department of Hepatopancreatobiliary Surgery, The Affiliated Hospital of Qinghai University, Xining 810001, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wanyang","family":"Li","sequence":"additional","affiliation":[{"name":"Beijing Key Laboratory of the Innovative Development of Functional Staple and the Nutritional Intervention for Chronic Disease, Department of Clinical Nutrition, Department of Health Medicine, Peking Union Medical College Hospital, Peking Union Medical College, Chinese Academy of Medical Sciences, Beijing 100730, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mingyao","family":"Sun","sequence":"additional","affiliation":[{"name":"Beijing Key Laboratory of the Innovative Development of Functional Staple and the Nutritional Intervention for Chronic Disease, Department of Clinical Nutrition, Department of Health Medicine, Peking Union Medical College Hospital, Peking Union Medical College, Chinese Academy of Medical Sciences, Beijing 100730, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hongyuan","family":"Cui","sequence":"additional","affiliation":[{"name":"Department of Hepato-Bilio-Pancreatic Surgery, Department of General Surgery, Beijing Hospital, National Center of Gerontology, Institute of Geriatric Medicine, Peking Union Medical College, Chinese Academy of Medical Sciences, Beijing 100730, China"},{"name":"Department of Hepatopancreatobiliary Surgery, The Affiliated Hospital of Qinghai University, Xining 810001, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wei","family":"Chen","sequence":"additional","affiliation":[{"name":"Beijing Key Laboratory of the Innovative Development of Functional Staple and the Nutritional Intervention for Chronic Disease, Department of Clinical Nutrition, Department of Health Medicine, Peking Union Medical College Hospital, Peking Union Medical College, Chinese Academy of Medical Sciences, Beijing 100730, China"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2024,10,17]]},"reference":[{"key":"ref_1","unstructured":"World Obesity Federation (2023, October 01). World Obesity Atlas 2023. Available online: https:\/\/data.worldobesity.org\/publications\/?cat=19."},{"key":"ref_2","unstructured":"World Health Organization (2023, October 01). Obesity and Overweight. Available online: https:\/\/www.who.int\/news-room\/fact-sheets\/detail\/obesity-and-overweight."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"110065","DOI":"10.1016\/j.foodres.2020.110065","article-title":"Highland barley: Chemical composition, bioactive compounds, health effects, and applications","volume":"140","author":"Obadi","year":"2021","journal-title":"Food Res. Int."},{"key":"ref_4","doi-asserted-by":"crossref","unstructured":"Kei, N., Wong, V.W.S., Lauw, S., You, L., and Cheung, P.C.K. (2023). Utilization of Food-Derived \u03b2-Glucans to Prevent and Treat Non-Alcoholic Fatty Liver Disease (NAFLD). Foods, 12.","DOI":"10.3390\/foods12173279"},{"key":"ref_5","doi-asserted-by":"crossref","unstructured":"\u0106orkovi\u0107, I., Ga\u0161o-Soka\u010d, D., Pichler, A., \u0160imunovi\u0107, J., and Kopjar, M. (2022). Dietary Polyphenols as Natural Inhibitors of \u03b1-Amylase and \u03b1-Glucosidase. Life, 12.","DOI":"10.3390\/life12111692"},{"key":"ref_6","doi-asserted-by":"crossref","unstructured":"Yang, W., Jiang, W., and Guo, S. (2023). Regulation of Macronutrients in Insulin Resistance and Glucose Homeostasis during Type 2 Diabetes Mellitus. Nutrients, 15.","DOI":"10.3390\/nu15214671"},{"key":"ref_7","doi-asserted-by":"crossref","unstructured":"Mahmoud, M.F., Abdelaal, S., Mohammed, H.O., El-Shazly, A.M., Daoud, R., El Raey, M.A., and Sobeh, M. (2021). Syzygium jambos extract mitigates pancreatic oxidative stress, inflammation and apoptosis and modulates hepatic IRS-2\/AKT\/GLUT4 signaling pathway in streptozotocin-induced diabetic rats. Biomed. Pharmacother., 142.","DOI":"10.1016\/j.biopha.2021.112085"},{"key":"ref_8","doi-asserted-by":"crossref","unstructured":"Fan, C., Liang, W., Wei, M., Gou, X., Han, S., and Bai, J. (2020). Effects of D-chiro-inositol on glucose metabolism in db\/db mice and the associated underlying mechanisms. Front. Pharmacol., 11.","DOI":"10.3389\/fphar.2020.00354"},{"key":"ref_9","doi-asserted-by":"crossref","unstructured":"Zhao, H., Lu, J., He, F., Wang, M., Yan, Y., Chen, B., Xie, D., Xu, C., Wang, Q., and Liu, W. (2022). Hyperuricemia contributes to glucose intolerance of hepatic inflammatory macrophages and impairs the insulin signaling pathway via IRS2-proteasome degradation. Front. Immunol., 13.","DOI":"10.3389\/fimmu.2022.931087"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"120907","DOI":"10.1016\/j.lfs.2022.120907","article-title":"A bovine milk-derived peptide ameliorates alloxan-injured pancreatic \u03b2 cells through IRS2\/PI3K\/Akt signaling","volume":"308","author":"Huang","year":"2022","journal-title":"Life Sci."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"1013","DOI":"10.2147\/DMSO.S206867","article-title":"Liraglutide ameliorates nonalcoholic fatty liver disease in diabetic mice via the IRS2\/PI3K\/Akt signaling pathway","volume":"12","author":"Yang","year":"2019","journal-title":"Diabetes Metab. Syndr. Obes."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"112863","DOI":"10.1016\/j.jep.2020.112863","article-title":"Agriophyllum oligosaccharides ameliorate hepatic injury in type 2 diabetic db\/db mice targeting INS-R\/IRS-2\/PI3K\/AKT\/PPAR-\u03b3\/Glut4 signal pathway","volume":"257","author":"Bao","year":"2020","journal-title":"J. Ethnopharmacol."},{"key":"ref_13","doi-asserted-by":"crossref","unstructured":"Yu, C., Luo, X., Zhan, X., Hao, J., Zhang, L., Song, Y.-B.L., Shen, C., and Dong, M. (2018). Comparative metabolomics reveals the metabolic variations between two endangered Taxus species (T. fuana and T. yunnanensis) in the Himalayas. BMC Plant Biol., 18.","DOI":"10.1186\/s12870-018-1412-4"},{"key":"ref_14","doi-asserted-by":"crossref","unstructured":"Li, Y., Fang, J., Qi, X., Lin, M., Zhong, Y., Sun, L., and Cui, W. (2018). Combined analysis of the fruit metabolome and transcriptome reveals candidate genes involved in flavonoid biosynthesis in Actinidia arguta. Int. J. Mol. Sci., 19.","DOI":"10.3390\/ijms19051471"},{"key":"ref_15","doi-asserted-by":"crossref","unstructured":"Li, X., Suo, J., Huang, X., Dai, H., Bian, H., Zhu, M., Lin, W., and Han, N. (2021). Whole grain Qingke attenuates HFD-induced obesity in mice with alterations in gut microbiota and metabolite profile. Front. Nutr., 8.","DOI":"10.3389\/fnut.2021.761727"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"11735","DOI":"10.1021\/acs.jafc.0c04780","article-title":"Highland barley whole grain (Hordeum vulgare L.) ameliorates hyperlipidemia by modulating cecal microbiota, miRNAs, and AMPK pathways in leptin receptor-deficient db\/db mice","volume":"68","author":"Deng","year":"2020","journal-title":"J. Agric. Food Chem."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"9535","DOI":"10.1039\/D0FO01990A","article-title":"IRS-1\/PI3K\/Akt pathway and miRNAs are involved in whole grain highland barley (Hordeum vulgare L.) ameliorating hyperglycemia of db\/db mice","volume":"11","author":"Deng","year":"2020","journal-title":"Food Funct."},{"key":"ref_18","doi-asserted-by":"crossref","unstructured":"Li, S., Wang, M., Li, C., Meng, Q., Meng, Y., Ying, J., Bai, S., Shen, Q., and Xue, Y. (2022). Beneficial effects of partly milled highland barley on the prevention of HFD-induced glycometabolic disorder and the modulation of gut microbiota in mice. Nutrients, 14.","DOI":"10.3390\/nu14040762"},{"key":"ref_19","doi-asserted-by":"crossref","unstructured":"Alaaeldin, R., Abdel-Rahman, I.A.M., Hassan, H.A., Youssef, N., Allam, A.E., Abdelwahab, S.F., Zhao, Q.-L., and Fathy, M. (2021). Carpachromene ameliorates insulin resistance in HepG2 cells via modulating IR\/IRS1\/PI3k\/Akt\/GSK3\/FoxO1 pathway. Molecules, 26.","DOI":"10.3390\/molecules26247629"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"e2100454","DOI":"10.1002\/mnfr.202100454","article-title":"Procyanidin B1 and p-Coumaric Acid from Highland Barley Grain Showed Synergistic Effect on Modulating Glucose Metabolism via IRS-1\/PI3K\/Akt Pathway","volume":"65","author":"Liu","year":"2021","journal-title":"Mol. Nutr. Food Res."},{"key":"ref_21","doi-asserted-by":"crossref","unstructured":"Zhao, Q., Hou, D., Fu, Y., Xue, Y., Guan, X., and Shen, Q. (2021). Adzuki Bean Alleviates Obesity and Insulin Resistance Induced by a High-Fat Diet and Modulates Gut Microbiota in Mice. Nutrients, 13.","DOI":"10.3390\/nu13093240"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"10075","DOI":"10.1021\/acs.jafc.3c02179","article-title":"Effects on Diabetic Mice of Consuming Lipid Extracted from Foxtail Millet (Setaria italica): Gut Microbiota Analysis and Serum Metabolomics","volume":"71","author":"Wang","year":"2023","journal-title":"J. Agric. Food Chem."},{"key":"ref_23","doi-asserted-by":"crossref","unstructured":"Hammad, M.M., Channanath, A.M., Abu-Farha, M., Rahman, A., Al Khairi, I., Cherian, P., Alramah, T., Alam-Eldin, N., Al-Mulla, F., and Thanaraj, T.A. (2023). Adolescent obesity and ANGPTL8: Correlations with high sensitivity C-reactive protein, leptin, and chemerin. Front. Endocrinol., 14.","DOI":"10.3389\/fendo.2023.1314211"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"3719","DOI":"10.1007\/s11033-021-06270-8","article-title":"ANGPTL8 roles in proliferation, metabolic diseases, hypothyroidism, polycystic ovary syndrome, and signaling pathways","volume":"48","author":"Navaeian","year":"2021","journal-title":"Mol. Biol. Rep."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"41","DOI":"10.1016\/j.jare.2022.08.006","article-title":"ANGPTL8 accelerates liver fibrosis mediated by HFD-induced inflammatory activity via LILRB2\/ERK signaling pathways","volume":"47","author":"Zhang","year":"2023","journal-title":"J. Adv. Res."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"100166","DOI":"10.1016\/j.jlr.2021.100166","article-title":"Apolipoprotein F concentration, activity, and the properties of LDL controlling ApoF activation in hyperlipidemic plasma","volume":"63","author":"Morton","year":"2022","journal-title":"J. Lipid Res."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"154703","DOI":"10.1016\/j.phymed.2023.154703","article-title":"Targeting mTOR\/YY1 signaling pathway by quercetin through CYP7A1-mediated cholesterol-to-bile acids conversion alleviated type 2 diabetes mellitus induced hepatic lipid accumulation","volume":"113","author":"Yang","year":"2023","journal-title":"Phytomedicine"},{"key":"ref_28","doi-asserted-by":"crossref","unstructured":"Yu Cai Lim, M., and Kiat Ho, H. (2024). Pharmacological modulation of cholesterol 7\u03b1-hydroxylase (CYP7A1) as a therapeutic strategy for hypercholesterolemia. Biochem. Pharmacol., 220.","DOI":"10.1016\/j.bcp.2023.115985"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"6882","DOI":"10.1002\/fsn3.2600","article-title":"Lactobacillus mediates the expression of NPC1L1, CYP7A1, and ABCG5 genes to regulate cholesterol","volume":"9","author":"Cao","year":"2021","journal-title":"Food Sci. Nutr."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"71","DOI":"10.1016\/j.cytogfr.2021.11.002","article-title":"Pathophysiological role of growth differentiation factor 15 (GDF15) in obesity, cancer, and cachexia","volume":"64","author":"Siddiqui","year":"2022","journal-title":"Cytokine Growth Factor Rev."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"1535","DOI":"10.1007\/s00424-020-02459-1","article-title":"GDF15, an update of the physiological and pathological roles it plays: A review","volume":"472","author":"Assadi","year":"2020","journal-title":"Pflug. Arch."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"1410","DOI":"10.1002\/mc.23024","article-title":"MARVELD1 interacting with catalase regulates reactive oxygen species metabolism and mediates the sensitivity to chemotherapeutic drugs in epithelial tumors of the reproductive system","volume":"58","author":"Zhang","year":"2019","journal-title":"Mol. Carcinog."},{"key":"ref_33","doi-asserted-by":"crossref","unstructured":"Kim, Y.C., Qi, M., Dong, X., Seok, S., Sun, H., Kemper, B., Fu, T., and Kemper, J.K. (2023). Transgenic mice lacking FGF15\/19-SHP phosphorylation display altered bile acids and gut bacteria, promoting nonalcoholic fatty liver disease. J. Biol. Chem., 299.","DOI":"10.1016\/j.jbc.2023.104946"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"100454","DOI":"10.1016\/j.jlr.2023.100454","article-title":"Deletion of hepatic small heterodimer partner ameliorates development of nonalcoholic steatohepatitis in mice","volume":"64","author":"Lee","year":"2023","journal-title":"J. Lipid Res."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"2020","DOI":"10.1111\/jcmm.14108","article-title":"Pex11a deficiency causes dyslipidaemia and obesity in mice","volume":"23","author":"Chen","year":"2019","journal-title":"J. Cell. Mol. Med."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"165","DOI":"10.1111\/jdi.13334","article-title":"Correlation analysis of microribonucleic acid-155 and microribonucleic acid-29 with type 2 diabetes mellitus, and the prediction and verification of target genes","volume":"12","author":"Zhu","year":"2021","journal-title":"J. Diabetes Investig."},{"key":"ref_37","doi-asserted-by":"crossref","unstructured":"Wang, H., Wang, J., Zhu, Y., Yan, H., and Lu, Y. (2021). Effects of Different Intensity Exercise on Glucose Metabolism and Hepatic IRS\/PI3K\/AKT Pathway in SD Rats Exposed with TCDD. Int. J. Environ. Res. Public Health, 18.","DOI":"10.3390\/ijerph182413141"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"7629","DOI":"10.1021\/acs.jafc.1c01813","article-title":"Flavonoids from whole-grain oat alleviated HFD-induced hyperlipidemia via regulating bile acid metabolism and gut microbiota in mice","volume":"69","author":"Duan","year":"2021","journal-title":"J. Agric. Food Chem."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"109297","DOI":"10.1016\/j.foodres.2020.109297","article-title":"Serum metabolomics analysis of the intervention effect of whole grain oats on insulin resistance induced by HFD in rats","volume":"135","author":"Zhao","year":"2020","journal-title":"Food Res. Int."},{"key":"ref_40","doi-asserted-by":"crossref","unstructured":"Wang, Y., Qi, W., Guo, X., Song, G., Pang, S., Fang, W., and Peng, Z. (2022). Effects of oats, tartary buckwheat, and foxtail millet supplementation on lipid metabolism, oxido-inflammatory responses, gut microbiota, and colonic SCFA composition in HFD fed rats. Nutrients, 14.","DOI":"10.3390\/nu14132760"}],"container-title":["Nutrients"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2072-6643\/16\/20\/3518\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T16:15:13Z","timestamp":1760112913000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2072-6643\/16\/20\/3518"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,10,17]]},"references-count":40,"journal-issue":{"issue":"20","published-online":{"date-parts":[[2024,10]]}},"alternative-id":["nu16203518"],"URL":"https:\/\/doi.org\/10.3390\/nu16203518","relation":{},"ISSN":["2072-6643"],"issn-type":[{"value":"2072-6643","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,10,17]]}}}