Autocrine/paracrine fibroblast growth factor 1 (FGF1) enhances systemic lipid metabolism in rainbow trout fed with a high-fat diet by elevating uridine levels through the AMPK signaling pathway and activating the upp2 promoter via irf1
Fibroblast growth factor 1 (FGF1) is recognized for its role in regulating vertebrate energy metabolism, yet its impact on metabolic fatty liver disease in fish remains unexamined. This study investigates the regulatory mechanism of the autocrine/paracrine cytokine FGF1 on systemic lipid metabolism...
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| creator | Yu, Huixia Mo, Haolin An, Xiaoran Yao, Mingxing Gao, Jiuwei Yu, Jiajia Xiong, Dongmei Liu, Haixia Li, Yang Wang, Lixin |
| description | Fibroblast growth factor 1 (FGF1) is recognized for its role in regulating vertebrate energy metabolism, yet its impact on metabolic fatty liver disease in fish remains unexamined. This study investigates the regulatory mechanism of the autocrine/paracrine cytokine FGF1 on systemic lipid metabolism in rainbow trout (Oncorhynchus mykiss) subjected to a high-fat diet (HFD). Experimental fish (540 in total) were divided between two dietary groups (low-fat diet (LFD) and HFD) and categorized into three treatment groups: LFD + PBS (LFD injected with PBS), HFD + PBS (HFD injected with PBS), and HFD + rFGF1 (HFD injected with recombinant FGF1 protein). Over a 6-week period on the HFD, rainbow trout demonstrated weight gain and signs of metabolic dysregulation. However, compared to the HFD + PBS group, exogenous rFGF1 administration significantly lowered hepatosomatic index (HSI), whole-body, muscle, and liver crude fat content, hepatic vacuole formation, serum triglyceride (TG), serum LDL-c, and the expression levels of fatty acid synthesis (fas) and transport genes (cd36, fatp6), while elevating HDL-c and the expression levels of fatty acid oxidation genes (cpt1a, pparα, and acox1) (P 0.05). Serum metabolomic analysis indicated that rFGF1 significantly elevated serum uridine levels (P |
| doi_str_mv | 10.1016/j.aquaculture.2024.741885 |
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•rFGF1 ameliorated ectopic lipid deposition in rainbow trout caused by a high-fat diet.•rFGF1 significantly increased serum uridine levels.•Uridine effectively improves lipid metabolism in hepatocytes•rFGF1 increased the flux of uridine synthesis through the AMPK signaling pathway•rFGF1 partially inhibits uridine breakdown by downregulating irf1 and causing its impaired binding to the promoter of upp2.</description><identifier>ISSN: 0044-8486</identifier><identifier>DOI: 10.1016/j.aquaculture.2024.741885</identifier><language>eng</language><publisher>Elsevier B.V</publisher><subject>AMPK pathway ; aquaculture ; autocrine signaling ; beta oxidation ; biosynthesis ; blood serum ; body weight ; catabolism ; crude fat ; cytokines ; energy metabolism ; fatty acids ; fatty liver ; Fibroblast growth factor 1 ; hepatosomatic index ; High-fat diet ; interferon regulatory factor-1 ; liver ; low fat diet ; metabolomics ; muscles ; Oncorhynchus mykiss ; phosphorylase ; Rainbow trout ; transcription (genetics) ; triacylglycerols ; Uridine ; vacuoles ; weight gain</subject><ispartof>Aquaculture, 2025-02, Vol.596, p.741885, Article 741885</ispartof><rights>2024 Elsevier B.V.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><cites>FETCH-LOGICAL-c228t-4323ee9554318fc5f4c84a91744ec40080d80d5e6d40684d46142de0090edaaf3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://www.sciencedirect.com/science/article/pii/S0044848624013474$$EHTML$$P50$$Gelsevier$$H</linktohtml><link.rule.ids>314,776,780,3537,27901,27902,65306</link.rule.ids></links><search><creatorcontrib>Yu, Huixia</creatorcontrib><creatorcontrib>Mo, Haolin</creatorcontrib><creatorcontrib>An, Xiaoran</creatorcontrib><creatorcontrib>Yao, Mingxing</creatorcontrib><creatorcontrib>Gao, Jiuwei</creatorcontrib><creatorcontrib>Yu, Jiajia</creatorcontrib><creatorcontrib>Xiong, Dongmei</creatorcontrib><creatorcontrib>Liu, Haixia</creatorcontrib><creatorcontrib>Li, Yang</creatorcontrib><creatorcontrib>Wang, Lixin</creatorcontrib><title>Autocrine/paracrine fibroblast growth factor 1 (FGF1) enhances systemic lipid metabolism in rainbow trout fed with a high-fat diet by elevating uridine levels through the AMPK signaling pathway and activating the upp2 promoter via irf1</title><title>Aquaculture</title><description>Fibroblast growth factor 1 (FGF1) is recognized for its role in regulating vertebrate energy metabolism, yet its impact on metabolic fatty liver disease in fish remains unexamined. This study investigates the regulatory mechanism of the autocrine/paracrine cytokine FGF1 on systemic lipid metabolism in rainbow trout (Oncorhynchus mykiss) subjected to a high-fat diet (HFD). Experimental fish (540 in total) were divided between two dietary groups (low-fat diet (LFD) and HFD) and categorized into three treatment groups: LFD + PBS (LFD injected with PBS), HFD + PBS (HFD injected with PBS), and HFD + rFGF1 (HFD injected with recombinant FGF1 protein). Over a 6-week period on the HFD, rainbow trout demonstrated weight gain and signs of metabolic dysregulation. However, compared to the HFD + PBS group, exogenous rFGF1 administration significantly lowered hepatosomatic index (HSI), whole-body, muscle, and liver crude fat content, hepatic vacuole formation, serum triglyceride (TG), serum LDL-c, and the expression levels of fatty acid synthesis (fas) and transport genes (cd36, fatp6), while elevating HDL-c and the expression levels of fatty acid oxidation genes (cpt1a, pparα, and acox1) (P < 0.05), thereby alleviating HFD-induced lipid accumulation without a significant impact on body weight (P > 0.05). Serum metabolomic analysis indicated that rFGF1 significantly elevated serum uridine levels (P < 0.05), with uridine demonstrating a capacity to regulate hepatocyte lipid metabolism effectively. Furthermore, rFGF1 was shown to enhance hepatic uridine biosynthesis through the AMPK signaling pathway, concurrently modulating uridine catabolism by downregulating interferon regulatory factor 1 (irf1) and altering its transcriptional control of uridine phosphorylase 2 (upp2). These findings suggest that rFGF1 mitigates hepatic lipid accumulation in rainbow trout under an HFD by promoting uridine synthesis via the AMPK pathway and partially inhibiting uridine catabolism through IRF1-UPP2 signaling.
•rFGF1 ameliorated ectopic lipid deposition in rainbow trout caused by a high-fat diet.•rFGF1 significantly increased serum uridine levels.•Uridine effectively improves lipid metabolism in hepatocytes•rFGF1 increased the flux of uridine synthesis through the AMPK signaling pathway•rFGF1 partially inhibits uridine breakdown by downregulating irf1 and causing its impaired binding to the promoter of upp2.</description><subject>AMPK pathway</subject><subject>aquaculture</subject><subject>autocrine signaling</subject><subject>beta oxidation</subject><subject>biosynthesis</subject><subject>blood serum</subject><subject>body weight</subject><subject>catabolism</subject><subject>crude fat</subject><subject>cytokines</subject><subject>energy metabolism</subject><subject>fatty acids</subject><subject>fatty liver</subject><subject>Fibroblast growth factor 1</subject><subject>hepatosomatic index</subject><subject>High-fat diet</subject><subject>interferon regulatory factor-1</subject><subject>liver</subject><subject>low fat diet</subject><subject>metabolomics</subject><subject>muscles</subject><subject>Oncorhynchus mykiss</subject><subject>phosphorylase</subject><subject>Rainbow trout</subject><subject>transcription (genetics)</subject><subject>triacylglycerols</subject><subject>Uridine</subject><subject>vacuoles</subject><subject>weight gain</subject><issn>0044-8486</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2025</creationdate><recordtype>article</recordtype><recordid>eNqNkUGP0zAQhXMAiWWX_zDclkO7duqk6bGq6ILYFRzgbE3sSTJVEmdtp1V_M38Cl-6BI9JIM7Lee3ryl2UfpVhKIcuHwxJfZjRzH2dPy1zkarlWsqqKN9mNEEotKlWV77L3IRyEEGVZyJvs93aOznge6WFCj38vaLj2ru4xRGi9O8UOGjTReZBwv3_cy09AY4ejoQDhHCINbKDniS0MFLF2PYcBeASPPNbuBNG7OUJDFk6cwhA6brtFgxEsU4T6DNTTESOPLcye7aVDeqA-QOySt-3SJtg-__gGgdsR-4tywtid8Aw4Wkj1-DXgopynKYfJu8FF8nBkBPaNvMveNtgH-vC6b7Nf-88_d18WT98fv-62TwuT51VcqFW-ItoUhVrJqjFFo0ylcCPXSpFRQlTCpimotEqUlbKqlCq3JMRGkEVsVrfZ_TU3NXiZKUQ9cDDU9ziSm4NeyULJUhTrIkk3V6nxLgRPjZ48D-jPWgp9gaoP-h-o-gJVX6Em7-7qTf9ERyavg2FKVCx7MlFbx_-R8gdJmrhO</recordid><startdate>20250215</startdate><enddate>20250215</enddate><creator>Yu, Huixia</creator><creator>Mo, Haolin</creator><creator>An, Xiaoran</creator><creator>Yao, Mingxing</creator><creator>Gao, Jiuwei</creator><creator>Yu, Jiajia</creator><creator>Xiong, Dongmei</creator><creator>Liu, Haixia</creator><creator>Li, Yang</creator><creator>Wang, Lixin</creator><general>Elsevier B.V</general><scope>AAYXX</scope><scope>CITATION</scope><scope>7S9</scope><scope>L.6</scope></search><sort><creationdate>20250215</creationdate><title>Autocrine/paracrine fibroblast growth factor 1 (FGF1) enhances systemic lipid metabolism in rainbow trout fed with a high-fat diet by elevating uridine levels through the AMPK signaling pathway and activating the upp2 promoter via irf1</title><author>Yu, Huixia ; Mo, Haolin ; An, Xiaoran ; Yao, Mingxing ; Gao, Jiuwei ; Yu, Jiajia ; Xiong, Dongmei ; Liu, Haixia ; Li, Yang ; Wang, Lixin</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c228t-4323ee9554318fc5f4c84a91744ec40080d80d5e6d40684d46142de0090edaaf3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2025</creationdate><topic>AMPK pathway</topic><topic>aquaculture</topic><topic>autocrine signaling</topic><topic>beta oxidation</topic><topic>biosynthesis</topic><topic>blood serum</topic><topic>body weight</topic><topic>catabolism</topic><topic>crude fat</topic><topic>cytokines</topic><topic>energy metabolism</topic><topic>fatty acids</topic><topic>fatty liver</topic><topic>Fibroblast growth factor 1</topic><topic>hepatosomatic index</topic><topic>High-fat diet</topic><topic>interferon regulatory factor-1</topic><topic>liver</topic><topic>low fat diet</topic><topic>metabolomics</topic><topic>muscles</topic><topic>Oncorhynchus mykiss</topic><topic>phosphorylase</topic><topic>Rainbow trout</topic><topic>transcription (genetics)</topic><topic>triacylglycerols</topic><topic>Uridine</topic><topic>vacuoles</topic><topic>weight gain</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Yu, Huixia</creatorcontrib><creatorcontrib>Mo, Haolin</creatorcontrib><creatorcontrib>An, Xiaoran</creatorcontrib><creatorcontrib>Yao, Mingxing</creatorcontrib><creatorcontrib>Gao, Jiuwei</creatorcontrib><creatorcontrib>Yu, Jiajia</creatorcontrib><creatorcontrib>Xiong, Dongmei</creatorcontrib><creatorcontrib>Liu, Haixia</creatorcontrib><creatorcontrib>Li, Yang</creatorcontrib><creatorcontrib>Wang, Lixin</creatorcontrib><collection>CrossRef</collection><collection>AGRICOLA</collection><collection>AGRICOLA - Academic</collection><jtitle>Aquaculture</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Yu, Huixia</au><au>Mo, Haolin</au><au>An, Xiaoran</au><au>Yao, Mingxing</au><au>Gao, Jiuwei</au><au>Yu, Jiajia</au><au>Xiong, Dongmei</au><au>Liu, Haixia</au><au>Li, Yang</au><au>Wang, Lixin</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Autocrine/paracrine fibroblast growth factor 1 (FGF1) enhances systemic lipid metabolism in rainbow trout fed with a high-fat diet by elevating uridine levels through the AMPK signaling pathway and activating the upp2 promoter via irf1</atitle><jtitle>Aquaculture</jtitle><date>2025-02-15</date><risdate>2025</risdate><volume>596</volume><spage>741885</spage><pages>741885-</pages><artnum>741885</artnum><issn>0044-8486</issn><abstract>Fibroblast growth factor 1 (FGF1) is recognized for its role in regulating vertebrate energy metabolism, yet its impact on metabolic fatty liver disease in fish remains unexamined. This study investigates the regulatory mechanism of the autocrine/paracrine cytokine FGF1 on systemic lipid metabolism in rainbow trout (Oncorhynchus mykiss) subjected to a high-fat diet (HFD). Experimental fish (540 in total) were divided between two dietary groups (low-fat diet (LFD) and HFD) and categorized into three treatment groups: LFD + PBS (LFD injected with PBS), HFD + PBS (HFD injected with PBS), and HFD + rFGF1 (HFD injected with recombinant FGF1 protein). Over a 6-week period on the HFD, rainbow trout demonstrated weight gain and signs of metabolic dysregulation. However, compared to the HFD + PBS group, exogenous rFGF1 administration significantly lowered hepatosomatic index (HSI), whole-body, muscle, and liver crude fat content, hepatic vacuole formation, serum triglyceride (TG), serum LDL-c, and the expression levels of fatty acid synthesis (fas) and transport genes (cd36, fatp6), while elevating HDL-c and the expression levels of fatty acid oxidation genes (cpt1a, pparα, and acox1) (P < 0.05), thereby alleviating HFD-induced lipid accumulation without a significant impact on body weight (P > 0.05). Serum metabolomic analysis indicated that rFGF1 significantly elevated serum uridine levels (P < 0.05), with uridine demonstrating a capacity to regulate hepatocyte lipid metabolism effectively. Furthermore, rFGF1 was shown to enhance hepatic uridine biosynthesis through the AMPK signaling pathway, concurrently modulating uridine catabolism by downregulating interferon regulatory factor 1 (irf1) and altering its transcriptional control of uridine phosphorylase 2 (upp2). These findings suggest that rFGF1 mitigates hepatic lipid accumulation in rainbow trout under an HFD by promoting uridine synthesis via the AMPK pathway and partially inhibiting uridine catabolism through IRF1-UPP2 signaling.
•rFGF1 ameliorated ectopic lipid deposition in rainbow trout caused by a high-fat diet.•rFGF1 significantly increased serum uridine levels.•Uridine effectively improves lipid metabolism in hepatocytes•rFGF1 increased the flux of uridine synthesis through the AMPK signaling pathway•rFGF1 partially inhibits uridine breakdown by downregulating irf1 and causing its impaired binding to the promoter of upp2.</abstract><pub>Elsevier B.V</pub><doi>10.1016/j.aquaculture.2024.741885</doi></addata></record> |
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| subjects | AMPK pathway aquaculture autocrine signaling beta oxidation biosynthesis blood serum body weight catabolism crude fat cytokines energy metabolism fatty acids fatty liver Fibroblast growth factor 1 hepatosomatic index High-fat diet interferon regulatory factor-1 liver low fat diet metabolomics muscles Oncorhynchus mykiss phosphorylase Rainbow trout transcription (genetics) triacylglycerols Uridine vacuoles weight gain |
| title | Autocrine/paracrine fibroblast growth factor 1 (FGF1) enhances systemic lipid metabolism in rainbow trout fed with a high-fat diet by elevating uridine levels through the AMPK signaling pathway and activating the upp2 promoter via irf1 |
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