Fetal programming imprints a lipidomic signature of skeletal muscle in beef cattle offspring

Fetal programming imprints a lipidomic signature of skeletal muscle in beef cattle offspring | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Article Fetal programming imprints a lipidomic signature of skeletal muscle in beef cattle offspring Felipe Eguti de Carvalho, Guilherme Henrique Gebim Polizel, Artur Oliveira Rocha, and 6 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-9348529/v1 This work is licensed under a CC BY 4.0 License Status: Under Review Version 1 posted 7 You are reading this latest preprint version Abstract As membrane lipids modulate membrane structure and function, mitochondrial bioenergetics, and lipid-mediated signaling, we hypothesized that skeletal muscle lipidomics could capture fetal programming (FP) effects in beef cattle. Therefore, 28 Nellore bulls born to heifers managed under two gestational nutritional regimens were studied: non-programmed (NP; mineral supplementation) and fetal programming (FP; protein–energy supplementation). Longissimus thoracis muscle samples collected at 24 h postmortem were analyzed using a targeted lipidomics approach. Of the 3,437 Multiple reaction monitoring (MRM) transitions evaluated, 408 were selected for data analyses. After sum-normalization and Pareto scaling, the data were first explored using principal component analysis (PCA) and hierarchical clustering to characterize the overall structure of the lipidomic profiles. Group differences were subsequently examined by volcano filtering (P ≤ 0.05; |fold change| ≥ 1.5). Functional interpretations were integrated into a mechanistic index, the phosphatidylcholine:phosphatidylethanolamine (PC:PE) ratio, and pathway enrichment analysis. Neutral-lipid composition was assessed computationally by binning quantified triacylglycerol (TG) species by total acyl-chain carbon number and double-bond count to derive chain-length and unsaturation distributions. PCA revealed treatment-related structure with partial NP–FP overlap, consistent with distributed effects. Univariate contrasts using Welch’s t-test (P ≤ 0.05 |fold change| ≥ 1.5) enabled the identification of 10 differentially abundant lipids (DAL), nine higher in NP and one higher in FP, but none remained significant after false-discovery-rate (FDR) correction (q < 0.10). These DAL clustered in membrane/signaling classes [PC; PE, including plasmalogens, phosphatidylserine (PS), phosphatidylglycerol (PG), and sphingomyelin (SM)/ceramides; and DG], with a few TG species acting as sentinels. The PC:PE ratio tended to be higher in FP, consistent with reduced inner-mitochondrial-membrane curvature capacity. The pathway-based enrichment analysis revealed twenty significant pathways between NP and FP Nellore offspring, highlighting hydrolysis of lysophosphatidylcholine, biosynthesis of unsaturated fatty acids and beta-oxidation of pristanoyl-CoA. The TG chain-length and unsaturation distributions did not differ between groups. A minimal targeted panel of approximately 10 to 12 lipids, together with the PC:PE ratio, was proposed for practical discrimination and monitoring of NP and FP groups. FP imprints a membrane-centric lipidomic signature in Longissimus thoracis muscle while neutral-lipid pools remained stable, linking phospholipid remodeling and signaling lipids to mitochondrial organization. This signature is amenable to MRM-based validation and can be operationalized as an integrative readout to classify NP vs FP cohorts, guide gestational supplementation strategies, and anticipate meat-quality endpoints such as meet color stability, oxidative robustness, and shelf-life, thereby supporting reduced retail losses, more consistent product specifications, and improved return on investment at the beef production level. Biological sciences/Biochemistry Biological sciences/Biological techniques Biological sciences/Physiology lipidomics meat quality prenatal nutrition postmortem oxidative stability Full Text Additional Declarations No competing interests reported. Supplementary Files SupplementaryMaterials.docx Cite Share Download PDF Status: Under Review Version 1 posted Reviews received at journal 13 May, 2026 Reviewers agreed at journal 12 May, 2026 Reviewers agreed at journal 22 Apr, 2026 Reviewers invited by journal 21 Apr, 2026 Editor assigned by journal 21 Apr, 2026 Submission checks completed at journal 10 Apr, 2026 First submitted to journal 10 Apr, 2026 You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. Our growing team is made up of researchers and industry professionals working together to solve the most critical problems facing scientific publishing. Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-9348529","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Article","associatedPublications":[],"authors":[{"id":632009828,"identity":"c7761b44-a035-4d61-86b1-e9de8c1c7b67","order_by":0,"name":"Felipe Eguti de 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offspring","fulltext":[],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":false,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":false,"highlight":"","institution":"","isAcceptedByJournal":false,"isAuthorSuppliedPdf":true,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":true,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"scientific-reports","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"scirep","sideBox":"Learn more about [Scientific Reports](http://www.nature.com/srep/)","snPcode":"","submissionUrl":"","title":"Scientific Reports","twitterHandle":"","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"stoa","reportingPortfolio":"Scientific Reports","inReviewEnabled":true,"inReviewRevisionsEnabled":true},"keywords":"lipidomics, meat quality, prenatal nutrition, postmortem, oxidative stability","lastPublishedDoi":"10.21203/rs.3.rs-9348529/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-9348529/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003eAs membrane lipids modulate membrane structure and function, mitochondrial bioenergetics, and lipid-mediated signaling, we hypothesized that skeletal muscle lipidomics could capture fetal programming (FP) effects in beef cattle. Therefore, 28 Nellore bulls born to heifers managed under two gestational nutritional regimens were studied: non-programmed (NP; mineral supplementation) and fetal programming (FP; protein\u0026ndash;energy supplementation). \u003cem\u003eLongissimus thoracis\u003c/em\u003e muscle samples collected at 24 h postmortem were analyzed using a targeted lipidomics approach. Of the 3,437 Multiple reaction monitoring (MRM) transitions evaluated, 408 were selected for data analyses. After sum-normalization and Pareto scaling, the data were first explored using principal component analysis (PCA) and hierarchical clustering to characterize the overall structure of the lipidomic profiles. Group differences were subsequently examined by volcano filtering (P\u0026thinsp;\u0026le;\u0026thinsp;0.05; |fold change| \u0026ge; 1.5). Functional interpretations were integrated into a mechanistic index, the phosphatidylcholine:phosphatidylethanolamine (PC:PE) ratio, and pathway enrichment analysis. Neutral-lipid composition was assessed computationally by binning quantified triacylglycerol (TG) species by total acyl-chain carbon number and double-bond count to derive chain-length and unsaturation distributions. PCA revealed treatment-related structure with partial NP\u0026ndash;FP overlap, consistent with distributed effects. Univariate contrasts using Welch\u0026rsquo;s t-test (P\u0026thinsp;\u0026le;\u0026thinsp;0.05 |fold change| \u0026ge; 1.5) enabled the identification of 10 differentially abundant lipids (DAL), nine higher in NP and one higher in FP, but none remained significant after false-discovery-rate (FDR) correction (q\u0026thinsp;\u0026lt;\u0026thinsp;0.10). These DAL clustered in membrane/signaling classes [PC; PE, including plasmalogens, phosphatidylserine (PS), phosphatidylglycerol (PG), and sphingomyelin (SM)/ceramides; and DG], with a few TG species acting as sentinels. The PC:PE ratio tended to be higher in FP, consistent with reduced inner-mitochondrial-membrane curvature capacity. The pathway-based enrichment analysis revealed twenty significant pathways between NP and FP Nellore offspring, highlighting hydrolysis of lysophosphatidylcholine, biosynthesis of unsaturated fatty acids and beta-oxidation of pristanoyl-CoA. The TG chain-length and unsaturation distributions did not differ between groups. A minimal targeted panel of approximately 10 to 12 lipids, together with the PC:PE ratio, was proposed for practical discrimination and monitoring of NP and FP groups. FP imprints a membrane-centric lipidomic signature in \u003cem\u003eLongissimus thoracis\u003c/em\u003e muscle while neutral-lipid pools remained stable, linking phospholipid remodeling and signaling lipids to mitochondrial organization. This signature is amenable to MRM-based validation and can be operationalized as an integrative readout to classify NP vs FP cohorts, guide gestational supplementation strategies, and anticipate meat-quality endpoints such as meet color stability, oxidative robustness, and shelf-life, thereby supporting reduced retail losses, more consistent product specifications, and improved return on investment at the beef production level.\u003c/p\u003e","manuscriptTitle":"Fetal programming imprints a lipidomic signature of skeletal muscle in beef cattle offspring","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2026-04-30 19:44:43","doi":"10.21203/rs.3.rs-9348529/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"editorInvitedReview","content":"","date":"2026-05-13T05:15:14+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"153874336978676902289269817438304912585","date":"2026-05-12T08:28:22+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"155893587674011424441657844705856132886","date":"2026-04-22T08:55:14+00:00","index":"hide","fulltext":""},{"type":"reviewersInvited","content":"","date":"2026-04-21T14:48:35+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2026-04-21T06:31:34+00:00","index":"","fulltext":""},{"type":"checksComplete","content":"","date":"2026-04-10T19:06:36+00:00","index":"","fulltext":""},{"type":"submitted","content":"Scientific Reports","date":"2026-04-10T17:39:38+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"scientific-reports","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"scirep","sideBox":"Learn more about [Scientific Reports](http://www.nature.com/srep/)","snPcode":"","submissionUrl":"","title":"Scientific Reports","twitterHandle":"","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"stoa","reportingPortfolio":"Scientific Reports","inReviewEnabled":true,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"552a6efa-6b3a-48c1-a869-afc38930cb4b","owner":[],"postedDate":"April 30th, 2026","published":true,"recentEditorialEvents":[{"type":"editorInvitedReview","content":"","date":"2026-05-13T05:15:14+00:00","index":26,"fulltext":""},{"type":"reviewerAgreed","content":"153874336978676902289269817438304912585","date":"2026-05-12T08:28:22+00:00","index":25,"fulltext":""}],"rejectedJournal":[],"revision":"","amendment":"","status":"under-review","subjectAreas":[{"id":67271839,"name":"Biological sciences/Biochemistry"},{"id":67271840,"name":"Biological sciences/Biological techniques"},{"id":67271841,"name":"Biological sciences/Physiology"}],"tags":[],"updatedAt":"2026-04-30T19:44:44+00:00","versionOfRecord":[],"versionCreatedAt":"2026-04-30 19:44:43","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-9348529","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-9348529","identity":"rs-9348529","version":["v1"]},"buildId":"XKTyCvWXoU3ODBz1xrDgd","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}