{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,23]],"date-time":"2026-10-23T20:35:56Z","timestamp":1792787756028,"version":"4.5.0"},"reference-count":37,"publisher":"SAGE Publications","license":[{"start":{"date-parts":[[2026,9,24]],"date-time":"2026-09-24T00:00:00Z","timestamp":1790208000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.sagepub.com\/page\/policies\/text-and-data-mining-license"}],"funder":[{"name":"National Natural Science Foundation of China","award":["No.82204655"],"award-info":[{"award-number":["No.82204655"]}],"id":[{"id":"https:\/\/ror.org\/01h0zpd94","id-type":"ROR","asserted-by":"crossref"}]},{"name":"National Natural Science Foundation of China","award":["No.82460334"],"award-info":[{"award-number":["No.82460334"]}],"id":[{"id":"https:\/\/ror.org\/01h0zpd94","id-type":"ROR","asserted-by":"crossref"}]},{"name":"Key R&D and Transformation Projects in Tibet Autonomous Region","award":["XZ202401ZY0107"],"award-info":[{"award-number":["XZ202401ZY0107"]}]}],"content-domain":{"domain":["journals.sagepub.com"],"crossmark-restriction":true},"short-container-title":["High Altitude Medicine & Biology"],"abstract":"\n \n \n Zhang, Xiaoying, Jiajia Wu, Yuchan Zhang, Yuquan Xie, Qi Si, Shadi Li, and Yiwei Han. PPAR\u03b1 activation attenuates right ventricular hypertrophy by regulating myocardial glucose and lipid metabolism in high-altitude pulmonary hypertension\n in\u00a0vivo<\/jats:italic>\n and\n in vitro<\/jats:italic>\n .\n High Alt Med Biol.<\/jats:italic>\n 00:00\u201300, 2026.\n <\/jats:p>\n <\/jats:sec>\n \n Background:<\/jats:title>\n Right ventricular hypertrophy (RVH) and cardiac function are key prognostic determinants in patients with high-altitude pulmonary hypertension. Meanwhile, their initiation and progression are driven by disturbances in glucose and lipid metabolism in cardiomyocytes.<\/jats:p>\n <\/jats:sec>\n \n Objective:<\/jats:title>\n \n This study established an SU5416-associated hypobaric hypoxia\u2013induced RVH (H-RVH) rat model and a CoCl\n 2<\/jats:sub>\n -induced hypoxic cardiomyocyte model to explore glucose and lipid metabolism alterations and mechanisms.\n <\/jats:p>\n <\/jats:sec>\n \n Methods:<\/jats:title>\n The metabolomic cluster analysis of metabolites primarily focused on lipid metabolism, along with Kyoto Encyclopedia of Genes and Genomes\u2013enriched pathways, including glycolysis\/gluconeogenesis, glycerophospholipid metabolism, and the peroxisome proliferator\u2013activated receptor (PPAR) signaling pathway.<\/jats:p>\n <\/jats:sec>\n \n Results:<\/jats:title>\n \n Compared with the control group, glucose transporter-4 (GLUT-4) and pyruvate dehydrogenase (PDH) kinase were increased by 320% and 220% in H-RVH rats, respectively (\n p<\/jats:italic>\n < 0.05), whereas PDH and citrate synthase (CS) were decreased by 39% and 58%, respectively (\n p<\/jats:italic>\n < 0.05), collectively indicating a shift toward glycolysis and away from glucose oxidation. Seahorse Extracellular Flux (XF) assay revealed that basal glycolysis and compensatory glycolytic capacity were significantly elevated in the CoCl\n 2<\/jats:sub>\n -induced hypoxic cardiomyocyte model compared with the control group (288.5 \u00b1 9.82 vs. 344.1 \u00b1 10.24, 335.9 \u00b1 11.58 vs. 385.7 \u00b1 14.74,\n p<\/jats:italic>\n < 0.05). The expression levels of PPAR\u03b1 and carnitine palmitoyltransferase 1\u03b1 (CPT-1\u03b1) in the H-RVH group were 48% and 56% lower than those in the control group, respectively (\n p<\/jats:italic>\n < 0.05); acetyl-CoA and adenosine triphosphate (ATP) were also reduced (\n p<\/jats:italic>\n < 0.05). Fenofibrate mitigated CoCl\n 2<\/jats:sub>\n -induced hypoxic damage through 1.6-fold activation of PPAR\u03b1. Cardiac-specific PPAR\u03b1 overexpression via an adeno-associated virus (AAV9) effectively attenuated RVH, as evidenced by the reduction in Fulton\u2019s index (0.37 \u00b1 0.09 vs. 0.46 \u00b1 0.02,\n p<\/jats:italic>\n < 0.05), right ventricular anterior wall diastolic (RVAWd) (0.64 \u00b1 0.04 vs. 0.93 \u00b1 0.02,\n p<\/jats:italic>\n < 0.01) and RVAWs (0.68 \u00b1 0.05 vs. 0.97 \u00b1 0.02,\n p<\/jats:italic>\n < 0.01). In contrast, PPAR\u03b1 knockdown did not significantly alter the Fulton index but markedly increased both RVAWd (1.00 \u00b1 0.01 vs. 0.77 \u00b1 0.03,\n p<\/jats:italic>\n < 0.01) and RVAWs (1.00 \u00b1 0.02 vs. 0.70 \u00b1 0.05,\n p<\/jats:italic>\n < 0.01).\n <\/jats:p>\n <\/jats:sec>\n \n Conclusion:<\/jats:title>\n In this study, our findings demonstrate that PPAR\u03b1 exerts a protective effect against RVH, at least in part, by promoting fatty acid oxidation through upregulation of its downstream target proteins CPT-1 and acyl-CoA oxidase 1.<\/jats:p>\n <\/jats:sec>","DOI":"10.1177\/15578682261490525","type":"journal-article","created":{"date-parts":[[2026,9,24]],"date-time":"2026-09-24T07:44:56Z","timestamp":1790235896000},"update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":0,"title":["PPAR\u03b1 Activation Attenuates Right Ventricular Hypertrophy by Regulating Myocardial Glucose and Lipid Metabolism in High-Altitude Pulmonary Hypertension\n In Vivo<\/i>\n and\n In Vitro<\/i>"],"prefix":"10.1177","author":[{"ORCID":"https:\/\/orcid.org\/0009-0009-0232-1936","authenticated-orcid":false,"given":"Xiaoying","family":"Zhang","sequence":"first","affiliation":[{"name":"School of Medicine, Xizang Minzu University, Xianyang, China."},{"name":"Engineering Research Center of Tibetan Medicine Detection Technology, Ministry of Education, Xianyang, China."},{"name":"Joint Laboratory for Research on Active Components and Pharmacological Mechanism of Tibetan Materia Medica, Tibetan Medical Research Center of Tibet, Xianyang, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiajia","family":"Wu","sequence":"additional","affiliation":[{"name":"School of Medicine, Xizang Minzu University, Xianyang, China."},{"name":"Engineering Research Center of Tibetan Medicine Detection Technology, Ministry of Education, Xianyang, China."},{"name":"Joint Laboratory for Research on Active Components and Pharmacological Mechanism of Tibetan Materia Medica, Tibetan Medical Research Center of Tibet, Xianyang, China."},{"name":"School of Health and Nursing, Wuchang University of Technology, Wuhan, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuchan","family":"Zhang","sequence":"additional","affiliation":[{"name":"School of Medicine, Xizang Minzu University, Xianyang, China."},{"name":"Engineering Research Center of Tibetan Medicine Detection Technology, Ministry of Education, Xianyang, China."},{"name":"Joint Laboratory for Research on Active Components and Pharmacological Mechanism of Tibetan Materia Medica, Tibetan Medical Research Center of Tibet, Xianyang, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuquan","family":"Xie","sequence":"additional","affiliation":[{"name":"School of Medicine, Xizang Minzu University, Xianyang, China."},{"name":"Engineering Research Center of Tibetan Medicine Detection Technology, Ministry of Education, Xianyang, China."},{"name":"Joint Laboratory for Research on Active Components and Pharmacological Mechanism of Tibetan Materia Medica, Tibetan Medical Research Center of Tibet, Xianyang, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qi","family":"Si","sequence":"additional","affiliation":[{"name":"School of Medicine, Xizang Minzu University, Xianyang, China."},{"name":"Engineering Research Center of Tibetan Medicine Detection Technology, Ministry of Education, Xianyang, China."},{"name":"Joint Laboratory for Research on Active Components and Pharmacological Mechanism of Tibetan Materia Medica, Tibetan Medical Research Center of Tibet, Xianyang, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shadi","family":"Li","sequence":"additional","affiliation":[{"name":"School of Medicine, Kashi University, Kashi, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yiwei","family":"Han","sequence":"additional","affiliation":[{"name":"Xi\u2019an Jiaotong University Second Affiliated Hospital, Xi\u2019an, China."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"179","published-online":{"date-parts":[[2026,9,24]]},"reference":[{"key":"e_1_3_3_2_1","doi-asserted-by":"publisher","DOI":"10.1093\/cvr\/cvv105"},{"key":"e_1_3_3_3_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10554-025-03326-9"},{"key":"e_1_3_3_4_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M509890200"},{"key":"e_1_3_3_5_1","doi-asserted-by":"publisher","DOI":"10.3389\/fcell.2023.1105565"},{"key":"e_1_3_3_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajpath.2019.02.005"},{"key":"e_1_3_3_7_1","doi-asserted-by":"publisher","DOI":"10.1093\/cvr\/cvad100"},{"key":"e_1_3_3_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.chemphyslip.2023.105325"},{"key":"e_1_3_3_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.pupt.2020.101985"},{"key":"e_1_3_3_10_1","doi-asserted-by":"publisher","DOI":"10.1089\/ham.2024.0107"},{"key":"e_1_3_3_11_1","doi-asserted-by":"publisher","DOI":"10.7150\/ijms.107224"},{"key":"e_1_3_3_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jacc.2023.10.045"},{"key":"e_1_3_3_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jnutbio.2022.108975"},{"key":"e_1_3_3_14_1","doi-asserted-by":"publisher","DOI":"10.1183\/13993003.00879-2022"},{"key":"e_1_3_3_15_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.phymed.2022.154329"},{"key":"e_1_3_3_16_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00395-025-01123-y"},{"key":"e_1_3_3_17_1","doi-asserted-by":"publisher","DOI":"10.1161\/circresaha.112.268128"},{"key":"e_1_3_3_18_1","doi-asserted-by":"publisher","DOI":"10.1089\/ham.2005.6.147"},{"key":"e_1_3_3_19_1","doi-asserted-by":"publisher","DOI":"10.1186\/s40709-021-00147-4"},{"key":"e_1_3_3_20_1","doi-asserted-by":"publisher","DOI":"10.3390\/metabo13050615"},{"key":"e_1_3_3_21_1","doi-asserted-by":"publisher","DOI":"10.2147\/dddt.s297500"},{"key":"e_1_3_3_22_1","doi-asserted-by":"publisher","DOI":"10.1111\/bph.70222"},{"key":"e_1_3_3_23_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12967-025-07088-9"},{"key":"e_1_3_3_24_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms21176421"},{"key":"e_1_3_3_25_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00109-010-0679-1"},{"key":"e_1_3_3_26_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.yjmcc.2021.05.004"},{"key":"e_1_3_3_27_1","doi-asserted-by":"publisher","DOI":"10.1002\/pul2.12266"},{"key":"e_1_3_3_28_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jacbts.2022.03.017"},{"key":"e_1_3_3_29_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajplung.00217.2009"},{"key":"e_1_3_3_30_1","doi-asserted-by":"publisher","DOI":"10.1093\/cvr\/cvae231"},{"key":"e_1_3_3_31_1","doi-asserted-by":"publisher","DOI":"10.2147\/pgpm.s356206"},{"key":"e_1_3_3_32_1","doi-asserted-by":"publisher","DOI":"10.1093\/cvr\/cvad108"},{"key":"e_1_3_3_33_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.2102463118"},{"key":"e_1_3_3_34_1","article-title":"Research on rat models of hypobaric hypoxia-induced pulmonary hypertension","author":"T-T Ma YW","year":"2015","unstructured":"T-T Ma YW, , Zhou X-L, , Jiang H, et al. Research on rat models of hypobaric hypoxia-induced pulmonary hypertension. Eur Rev Med Pharmacol Sci 2015.","journal-title":"Eur Rev Med Pharmacol Sci"},{"key":"e_1_3_3_35_1","doi-asserted-by":"publisher","DOI":"10.1126\/sciadv.adk5184"},{"key":"e_1_3_3_36_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jtcvs.2020.08.011"},{"key":"e_1_3_3_37_1","doi-asserted-by":"publisher","DOI":"10.7150\/ijbs.86214"},{"issue":"06","key":"e_1_3_3_38_1","first-page":"1153","article-title":"Effects of fenofibrate on right ventricular hypertrophy in rats with high altitude heart disease and its mechanisms","volume":"41","author":"Zhang XY","year":"2025","unstructured":"Zhang XY, , Si Q, , Wu JJ, et al. Effects of fenofibrate on right ventricular hypertrophy in rats with high altitude heart disease and its mechanisms. Chinese Journal of Pathophysiology 2025;41(06):1153\u20131161.","journal-title":"Chinese Journal of Pathophysiology"}],"container-title":["High Altitude Medicine & Biology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/journals.sagepub.com\/doi\/pdf\/10.1177\/15578682261490525","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.sagepub.com\/doi\/full-xml\/10.1177\/15578682261490525","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.sagepub.com\/doi\/pdf\/10.1177\/15578682261490525","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,9,27]],"date-time":"2026-09-27T13:48:56Z","timestamp":1790516936000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.sagepub.com\/doi\/10.1177\/15578682261490525"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,9,24]]},"references-count":37,"alternative-id":["10.1177\/15578682261490525"],"URL":"https:\/\/doi.org\/10.1177\/15578682261490525","relation":{},"ISSN":["1527-0297","1557-8682"],"issn-type":[{"value":"1527-0297","type":"print"},{"value":"1557-8682","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,9,24]]},"article-number":"15578682261490525"}}