{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,31]],"date-time":"2026-03-31T14:53:51Z","timestamp":1774968831357,"version":"3.50.1"},"reference-count":33,"publisher":"Wiley","issue":"7","license":[{"start":{"date-parts":[[2023,6,1]],"date-time":"2023-06-01T00:00:00Z","timestamp":1685577600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82100950"],"award-info":[{"award-number":["82100950"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82170909"],"award-info":[{"award-number":["82170909"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100007219","name":"Natural Science Foundation of Shanghai","doi-asserted-by":"publisher","award":["22ZR1441100"],"award-info":[{"award-number":["22ZR1441100"]}],"id":[{"id":"10.13039\/100007219","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100018625","name":"Science and Technology Innovation Plan Of Shanghai Science and Technology Commission","doi-asserted-by":"publisher","award":["22Y31900600"],"award-info":[{"award-number":["22Y31900600"]}],"id":[{"id":"10.13039\/501100018625","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["faseb.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["The FASEB Journal"],"published-print":{"date-parts":[[2023,7]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Parenteral nutrition, received by many patients with intestinal failure, can induce hepatobiliary complications, which is termed as parenteral nutrition\u2010associated liver disease (PNALD). The spectrum of PNALD ranges from cholestasis and steatosis to fibrosis and cirrhosis. Although many factors contribute to the pathogenesis of PNALD, the underlying mechanisms remain unclear. In this study, we performed targeted metabolomics to characterize the metabolomic profile in neonatal piglets receiving total parenteral nutrition (TPN) or enteral nutrition (EN) for 1 or 2\u2009weeks. Overall, the metabolomic signature of TPN groups differed from EN groups at both time points. Among the 20 acylcarnitines identified, a majority of them were significantly reduced in TPN groups. KEGG pathway analysis showed that phenylalanine metabolism\u2010associated pathways were dysregulated accompanied by more progressive liver steatosis associated with TPN. Next, we evaluated phenylalanine catabolism and its association with fatty acid oxidation in piglets and rats with PNALD. We showed that the hepatic expression of phenylalanine\u2010degrading enzyme phenylalanine hydroxylase (PAH) was reduced and systemic phenylalanine levels were increased in both animal models of PNALD. Moreover, carnitine palmitoyltransferase 1A, a central regulator of fatty acid oxidation, was downregulated and its expression was negatively correlated with phenylalanine levels in TPN\u2010fed animals. To explore the effects of phenylalanine accumulation on lipid metabolism, we treated HepG2 cells with phenylalanine co\u2010cultured with sodium palmitate or soybean oil emulsion to induce lipid accumulation. We found that phenylalanine treatment exacerbated lipid accumulation by inhibiting fatty acid oxidation without affecting fatty acid synthesis. In summary, our findings establish a pathogenic role of increased phenylalanine levels in driving liver steatosis, linking dysregulation of phenylalanine catabolism with lipid accumulation in the context of PNALD.<\/jats:p>","DOI":"10.1096\/fj.202300261rr","type":"journal-article","created":{"date-parts":[[2023,6,1]],"date-time":"2023-06-01T11:13:16Z","timestamp":1685617996000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["Targeted metabolomics unravels altered phenylalanine levels in piglets receiving total parenteral nutrition"],"prefix":"10.1096","volume":"37","author":[{"given":"Lu","family":"Jiang","sequence":"first","affiliation":[{"name":"Division of Pediatric Gastroenterology and Nutrition Xinhua Hospital School of Medicine Shanghai Jiao Tong University  Shanghai China"},{"name":"Shanghai Key Laboratory of Pediatric Gastroenterology and Nutrition  Shanghai China"},{"name":"Shanghai Institute for Pediatric Research  Shanghai China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yang","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Pediatric Surgery Xinhua Hospital School of Medicine, Shanghai Jiao Tong University  Shanghai China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yongchang","family":"Zhou","sequence":"additional","affiliation":[{"name":"Shanghai Institute for Pediatric Research  Shanghai China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Qingyang","family":"Xu","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology Xinhua Hospital Shanghai Jiao Tong University School of Medicine  Shanghai China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Siyang","family":"Cheng","sequence":"additional","affiliation":[{"name":"Department of Pediatric Surgery Xinhua Hospital School of Medicine, Shanghai Jiao Tong University  Shanghai China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Junkai","family":"Yan","sequence":"additional","affiliation":[{"name":"Division of Pediatric Gastroenterology and Nutrition Xinhua Hospital School of Medicine Shanghai Jiao Tong University  Shanghai China"},{"name":"Shanghai Key Laboratory of Pediatric Gastroenterology and Nutrition  Shanghai China"},{"name":"Shanghai Institute for Pediatric Research  Shanghai China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yongtao","family":"Xiao","sequence":"additional","affiliation":[{"name":"Division of Pediatric Gastroenterology and Nutrition Xinhua Hospital School of Medicine Shanghai Jiao Tong University  Shanghai China"},{"name":"Shanghai Key Laboratory of Pediatric Gastroenterology and Nutrition  Shanghai China"},{"name":"Shanghai Institute for Pediatric Research  Shanghai China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lianshu","family":"Han","sequence":"additional","affiliation":[{"name":"Department of Pediatric Endocrinology\/Genetics Xinhua Hospital School of Medicine Shanghai Jiao Tong University  Shanghai China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ying","family":"Wang","sequence":"additional","affiliation":[{"name":"Division of Pediatric Gastroenterology and Nutrition Xinhua Hospital School of Medicine Shanghai Jiao Tong University  Shanghai China"},{"name":"Shanghai Key Laboratory of Pediatric Gastroenterology and Nutrition  Shanghai China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wei","family":"Cai","sequence":"additional","affiliation":[{"name":"Division of Pediatric Gastroenterology and Nutrition Xinhua Hospital School of Medicine Shanghai Jiao Tong University  Shanghai China"},{"name":"Shanghai Key Laboratory of Pediatric Gastroenterology and Nutrition  Shanghai China"},{"name":"Shanghai Institute for Pediatric Research  Shanghai China"},{"name":"Department of Pediatric Surgery Xinhua Hospital School of Medicine, Shanghai Jiao Tong University  Shanghai China"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2023,6]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.1177\/0115426506021003279"},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.1126\/scitranslmed.3006898"},{"key":"e_1_2_10_4_1","doi-asserted-by":"publisher","DOI":"10.1002\/hep.26360"},{"key":"e_1_2_10_5_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12072-020-10048-8"},{"key":"e_1_2_10_6_1","doi-asserted-by":"publisher","DOI":"10.1002\/jpen.2374"},{"key":"e_1_2_10_7_1","doi-asserted-by":"publisher","DOI":"10.3390\/metabo12070600"},{"key":"e_1_2_10_8_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpgi.00280.2011"},{"key":"e_1_2_10_9_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpgi.00193.2019"},{"key":"e_1_2_10_10_1","doi-asserted-by":"publisher","DOI":"10.1097\/MPG.0000000000003135"},{"key":"e_1_2_10_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jpedsurg.2020.06.035"},{"key":"e_1_2_10_12_1","first-page":"238","article-title":"Establishment of total parenteral nutrition model and study on intestinal barrier function in newborn Bama mini\u2010pig","volume":"28","author":"Liu Yang XY","year":"2021","journal-title":"Chin J Nat Med"},{"key":"e_1_2_10_13_1","doi-asserted-by":"publisher","DOI":"10.1021\/acs.analchem.0c04686"},{"key":"e_1_2_10_14_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-019-1742-x"},{"key":"e_1_2_10_15_1","doi-asserted-by":"publisher","DOI":"10.3748\/wjg.v23.i43.7705"},{"key":"e_1_2_10_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jcmgh.2021.12.003"},{"key":"e_1_2_10_17_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jpedsurg.2021.12.015"},{"key":"e_1_2_10_18_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0022-3476(79)80306-6"},{"key":"e_1_2_10_19_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0022-3476(95)70562-7"},{"key":"e_1_2_10_20_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbamcr.2016.01.023"},{"key":"e_1_2_10_21_1","doi-asserted-by":"publisher","DOI":"10.1159\/000243302"},{"key":"e_1_2_10_22_1","doi-asserted-by":"publisher","DOI":"10.1016\/0031-9384(96)00021-2"},{"key":"e_1_2_10_23_1","doi-asserted-by":"publisher","DOI":"10.1194\/jlr.M069526"},{"key":"e_1_2_10_24_1","doi-asserted-by":"publisher","DOI":"10.1053\/j.gastro.2009.08.016"},{"key":"e_1_2_10_25_1","doi-asserted-by":"publisher","DOI":"10.1038\/jp.2010.207"},{"key":"e_1_2_10_26_1","doi-asserted-by":"publisher","DOI":"10.3233\/JAD-210461"},{"key":"e_1_2_10_27_1","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCULATIONAHA.121.054204"},{"key":"e_1_2_10_28_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13578-023-00974-z"},{"key":"e_1_2_10_29_1","doi-asserted-by":"publisher","DOI":"10.1093\/jn\/137.6.1579S"},{"key":"e_1_2_10_30_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11695-008-9521-z"},{"key":"e_1_2_10_31_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-020-67971-x"},{"key":"e_1_2_10_32_1","doi-asserted-by":"publisher","DOI":"10.3390\/nu13020508"},{"key":"e_1_2_10_33_1","doi-asserted-by":"publisher","DOI":"10.1146\/annurev-animal-020518-115142"},{"key":"e_1_2_10_34_1","doi-asserted-by":"publisher","DOI":"10.1093\/jn\/136.10.2547"}],"container-title":["The FASEB Journal"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/faseb.onlinelibrary.wiley.com\/doi\/pdf\/10.1096\/fj.202300261RR","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,28]],"date-time":"2025-10-28T17:17:50Z","timestamp":1761671870000},"score":1,"resource":{"primary":{"URL":"https:\/\/faseb.onlinelibrary.wiley.com\/doi\/10.1096\/fj.202300261RR"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,6]]},"references-count":33,"journal-issue":{"issue":"7","published-print":{"date-parts":[[2023,7]]}},"alternative-id":["10.1096\/fj.202300261RR"],"URL":"https:\/\/doi.org\/10.1096\/fj.202300261rr","archive":["Portico"],"relation":{},"ISSN":["0892-6638","1530-6860"],"issn-type":[{"value":"0892-6638","type":"print"},{"value":"1530-6860","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,6]]},"assertion":[{"value":"2023-02-14","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2023-05-19","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2023-06-01","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e23014"}}