{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,16]],"date-time":"2026-09-16T16:27:37Z","timestamp":1789576057760,"version":"build-2803163510"},"reference-count":45,"publisher":"MDPI AG","issue":"7","license":[{"start":{"date-parts":[[2020,7,16]],"date-time":"2020-07-16T00:00:00Z","timestamp":1594857600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001807","name":"Funda\u00e7\u00e3o de Amparo \u00e0 Pesquisa do Estado de S\u00e3o Paulo","doi-asserted-by":"publisher","award":["#2014\/13334-7, #2017\/10809-2, #2017\/02739-4, 2019\/13937-7"],"award-info":[{"award-number":["#2014\/13334-7, #2017\/10809-2, #2017\/02739-4, 2019\/13937-7"]}],"id":[{"id":"10.13039\/501100001807","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100002322","name":"Coordena\u00e7\u00e3o de Aperfei\u00e7oamento de Pessoal de N\u00edvel Superior","doi-asserted-by":"publisher","award":["001"],"award-info":[{"award-number":["001"]}],"id":[{"id":"10.13039\/501100002322","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003593","name":"Conselho Nacional de Desenvolvimento Cient\u00edfico e Tecnol\u00f3gico","doi-asserted-by":"publisher","award":["grant number #302524\/2016-9"],"award-info":[{"award-number":["grant number #302524\/2016-9"]}],"id":[{"id":"10.13039\/501100003593","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Nutrients"],"abstract":"<jats:p>A maternal leucine-rich diet showed a positive effect on the gastrocnemius muscle of adult tumor-bearing offspring. To improve the understanding of the metabolic alterations of cancer cachexia and correlate this to preventive treatment, we evaluated the 1H NMR metabolic profiles from serum and gastrocnemius muscle samples of adult Wistar rats. These profiles were initially analyzed, and chemometrics tools were applied to investigate the following groups: C, control group; W, tumor-bearing group; L, the group without tumors and with a maternal leucine-rich diet; WL, the tumor-bearing group with a maternal leucine-rich diet. Tumor growth that led to a high protein breakdown in the W group was correlated to serum metabolites such as tyrosine, phenylalanine, histidine, glutamine, and tryptophan amino acids and uracil. Also, decreased muscle lactate, inversely to serum content, was found in the W group. Conversely, in the WL group, increased lactate in muscle and serum profiles was found, which could be correlated to the maternal diet effect. The muscle lipidomics and NAD+, NADP+, lysine, 4-aminohippurate, and glutamine metabolites pointed to modified energy metabolism and lower muscle mass loss in the WL group. In conclusion, this exploratory metabolomics analyses provided novel insights related to the Walker-256 tumor-bearing offspring metabolism modified by a maternal leucine-rich diet and the next steps in its investigation.<\/jats:p>","DOI":"10.3390\/nu12072106","type":"journal-article","created":{"date-parts":[[2020,7,16]],"date-time":"2020-07-16T10:54:46Z","timestamp":1594896886000},"page":"2106","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["Serum and Muscle 1H NMR-Based Metabolomics Profiles Reveal Metabolic Changes Influenced by a Maternal Leucine-Rich Diet in Tumor-Bearing Adult Offspring Rats"],"prefix":"10.3390","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4446-7924","authenticated-orcid":false,"given":"Nat\u00e1lia Angelo da Silva","family":"Miyaguti","sequence":"first","affiliation":[{"name":"Laboratory of Nutrition and Cancer, Department of Structural and Functional Biology, Biology Institute, University of Campinas (UNICAMP), Rua Monteiro Lobato, 255, Campinas, SP 13083862, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Danijela","family":"Stanisic","sequence":"additional","affiliation":[{"name":"Chemical Biology Laboratory, Organic Chemistry Department, Institute of Chemistry, University of Campinas (UNICAMP), Rua Josu\u00e9 de Castro, s\/n, Campinas, SP 13083970, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5635-7741","authenticated-orcid":false,"given":"Sarah Christine Pereira de","family":"Oliveira","sequence":"additional","affiliation":[{"name":"Laboratory of Nutrition and Cancer, Department of Structural and Functional Biology, Biology Institute, University of Campinas (UNICAMP), Rua Monteiro Lobato, 255, Campinas, SP 13083862, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9441-783X","authenticated-orcid":false,"given":"Gabriela Sales","family":"dos Santos","sequence":"additional","affiliation":[{"name":"Laboratory of Nutrition and Cancer, Department of Structural and Functional Biology, Biology Institute, University of Campinas (UNICAMP), Rua Monteiro Lobato, 255, Campinas, SP 13083862, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Beatriz Schincariol","family":"Manhe","sequence":"additional","affiliation":[{"name":"Laboratory of Nutrition and Cancer, Department of Structural and Functional Biology, Biology Institute, University of Campinas (UNICAMP), Rua Monteiro Lobato, 255, Campinas, SP 13083862, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2930-7332","authenticated-orcid":false,"given":"Ljubica","family":"Tasic","sequence":"additional","affiliation":[{"name":"Chemical Biology Laboratory, Organic Chemistry Department, Institute of Chemistry, University of Campinas (UNICAMP), Rua Josu\u00e9 de Castro, s\/n, Campinas, SP 13083970, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1713-756X","authenticated-orcid":false,"given":"Maria Cristina Cintra","family":"Gomes-Marcondes","sequence":"additional","affiliation":[{"name":"Laboratory of Nutrition and Cancer, Department of Structural and Functional Biology, Biology Institute, University of Campinas (UNICAMP), Rua Monteiro Lobato, 255, Campinas, SP 13083862, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2020,7,16]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Argil\u00e9s, J.M., Stemmler, B., L\u00f3pez-Soriano, F.J., and Busquets, S. (2018). Inter-tissue communication in cancer cachexia. Nat. Rev. Endocrinol.","DOI":"10.1038\/s41574-018-0123-0"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"489","DOI":"10.1016\/S1470-2045(10)70218-7","article-title":"Definition and classification of cancer cachexia: An international consensus","volume":"12","author":"Fearon","year":"2011","journal-title":"Lancet Oncol."},{"key":"ref_3","doi-asserted-by":"crossref","unstructured":"da Silva Miyaguti, N.A., de Oliveira, S.C.P., and Gomes-Marcondes, M.C.C. (2019). Maternal Leucine-Rich Diet Minimises Muscle Mass Loss in Tumour-bearing Adult Rat Offspring by Improving the Balance of Muscle Protein Synthesis and Degradation. Biomolecules, 9.","DOI":"10.3390\/biom9060229"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"23","DOI":"10.1385\/ENDO:19:1:23","article-title":"Transport and Metabolism of Amino Acids in Placenta","volume":"19","author":"Regnault","year":"2002","journal-title":"Endocrine"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1095\/biolreprod.112.107276","article-title":"Leucine-Rich Diet Improves the Serum Amino Acid Profile and Body Composition of Fetuses from Tumor-Bearing Pregnant Mice1","volume":"88","author":"Viana","year":"2013","journal-title":"Biol. Reprod."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"17048","DOI":"10.3390\/ijms160817048","article-title":"Milk\u2014A Nutrient System of Mammalian Evolution Promoting mTORC1-Dependent Translation","volume":"16","author":"Melnik","year":"2015","journal-title":"Int. J. Mol. Sci."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"e200","DOI":"10.1038\/oncsis.2016.3","article-title":"Understanding cachexia as a cancer metabolism syndrome","volume":"5","author":"Porporato","year":"2016","journal-title":"Oncogenesis"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"960","DOI":"10.1016\/j.cell.2017.02.004","article-title":"mTOR Signaling in Growth, Metabolism, and Disease","volume":"168","author":"Saxton","year":"2017","journal-title":"Cell"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"2134","DOI":"10.1016\/j.biocel.2005.03.010","article-title":"Ca(2+)-dependent proteolysis in muscle wasting","volume":"37","author":"Costelli","year":"2005","journal-title":"Int. J. Biochem. Cell Biol."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"153","DOI":"10.1016\/j.cmet.2012.06.011","article-title":"Cancer cachexia: Mediators, signaling, and metabolic pathways","volume":"16","author":"Fearon","year":"2012","journal-title":"Cell Metab."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"711","DOI":"10.1007\/s00394-014-0654-7","article-title":"Maternal diet, bioactive molecules, and exercising as reprogramming tools of metabolic programming","volume":"53","author":"Mathias","year":"2014","journal-title":"Eur. J. Nutr."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"2748","DOI":"10.3390\/nu7042748","article-title":"Considering maternal dietary modulators for epigenetic regulation and programming of the fetal epigenome","volume":"7","author":"Chango","year":"2015","journal-title":"Nutrients"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"205","DOI":"10.1615\/CritRevBiomedEng.2013007736","article-title":"Metabolomic Fingerprinting: Challenges and Opportunities","volume":"41","author":"Kosmides","year":"2013","journal-title":"Crit Rev. Biomed. Eng."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"1361","DOI":"10.1016\/j.peptides.2010.03.028","article-title":"Dietary l-leucine supplementation of lactating rats results in a tendency to increase lean\/fat ratio associated to lower orexigenic neuropeptide expression in hypothalamus","volume":"31","author":"Palou","year":"2010","journal-title":"Peptides"},{"key":"ref_15","doi-asserted-by":"crossref","unstructured":"L\u00f3pez, N., S\u00e1nchez, J., Palou, A., and Serra, F. (2018). Gender-associated impact of early leucine supplementation on adult predisposition to obesity in rats. Nutrients, 10.","DOI":"10.3390\/nu10010076"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"473","DOI":"10.1038\/nrd.2016.32","article-title":"Emerging applications of metabolomics in drug discovery and precision medicine","volume":"15","author":"Wishart","year":"2016","journal-title":"Nat. Rev. Drug Discov."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"92","DOI":"10.1016\/j.semcdb.2015.12.022","article-title":"Omics\/systems biology and cancer cachexia","volume":"54","author":"Gallagher","year":"2016","journal-title":"Semin. Cell Dev. Biol."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"181","DOI":"10.1097\/MCO.0000000000000363","article-title":"Omics and cachexia","volume":"20","author":"Twelkmeyer","year":"2017","journal-title":"Curr. Opin. Clin. Nutr. Metab. Care"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1038\/srep20683","article-title":"Diet-induced changes in maternal gut microbiota and metabolomic profiles influence programming of offspring obesity risk in rats","volume":"6","author":"Paul","year":"2016","journal-title":"Sci. Rep."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"811","DOI":"10.1038\/sj.bjc.6602425","article-title":"Trends in UK cancer trials: Results from the UK Coordinating Committee for Cancer Research National Register of Cancer Trials","volume":"92","author":"Vale","year":"2005","journal-title":"Br. J. Cancer"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"1939","DOI":"10.1093\/jn\/123.11.1939","article-title":"AIN-93 Purified Diets for Laboratory Rodents: Final Report of the American Institute of Nutrition Ad Hoc Writing Committee on the Reformulation of the AIN-76A Rodent Diet","volume":"123","author":"Reeves","year":"1993","journal-title":"J. Nutr."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"29","DOI":"10.1016\/j.nutres.2017.12.003","article-title":"Maternal nutritional supplementation with fish oil and\/or leucine improves hepatic function and antioxidant defenses, and minimizes cachexia indexes in Walker-256 tumor-bearing rats offspring","volume":"51","year":"2018","journal-title":"Nutr. Res."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"153","DOI":"10.1016\/B978-0-12-074901-0.50014-9","article-title":"Reproduction and breeding","volume":"Volume 1","author":"Baker","year":"1979","journal-title":"The Laboratory Rat"},{"key":"ref_24","first-page":"277","article-title":"Consequences of Walker 256 tumour growth for the placental\/foetal development in rats","volume":"5","author":"Curi","year":"1998","journal-title":"J. Cancer Res. Ther."},{"key":"ref_25","doi-asserted-by":"crossref","unstructured":"Viana, L.R., Canevarolo, R., Luiz, A.C.P., Soares, R.F., Lubaczeuski, C., de Matto Zeri, A.C., and Gomes-Marcondes, M.C.C. (2016). Leucine-rich diet alters the 1H-NMR based metabolomic profile without changing the Walker-256 tumour mass in rats. BMC Cancer, 16.","DOI":"10.1186\/s12885-016-2811-2"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"37","DOI":"10.1002\/nbm.740","article-title":"A comparison of cell and tissue extraction techniques using high-resolution 1H-NMR spectroscopy","volume":"15","author":"Harris","year":"2002","journal-title":"NMR Biomed."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"4281","DOI":"10.1021\/ac051632c","article-title":"Probabilistic quotient normalization as robust method to account for dilution of complex biological mixtures. Application in 1H NMR metabonomics","volume":"78","author":"Dieterle","year":"2006","journal-title":"Anal. Chem."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"469","DOI":"10.1021\/pr060594q","article-title":"Chemometrics in metabonomics","volume":"6","author":"Trygg","year":"2007","journal-title":"J. Proteome Res."},{"key":"ref_29","unstructured":"Wallace, H. (1989). Statistics for toxicologists. Principles and Methods of Toxicology, Raven Press Ltd.. [2nd ed.]."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"11766","DOI":"10.1039\/C4RA14128H","article-title":"NMR-based metabolomics reveals distinct pathways mediated by curcumin in cachexia mice bearing CT26 tumor","volume":"5","author":"Jun","year":"2015","journal-title":"RSC Adv."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"3015","DOI":"10.1039\/c3mb70134d","article-title":"Serum metabolic profiles reveal the effect of formoterol on cachexia in tumor-bearing mice","volume":"9","author":"Quanjun","year":"2013","journal-title":"Mol. Biosyst."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"787","DOI":"10.1007\/s11306-014-0760-9","article-title":"The Warburg effect: A balance of flux analysis","volume":"11","author":"Vaitheesvaran","year":"2015","journal-title":"Metabolomics"},{"key":"ref_33","first-page":"1","article-title":"Skeletal muscle metabolomics and blood biochemistry analysis reveal metabolic changes associated with dietary amino acid supplementation in dairy calves","volume":"8","author":"Yu","year":"2018","journal-title":"Sci. Rep."},{"key":"ref_34","first-page":"1","article-title":"Non-invasive urinary metabolomic profiling discriminates prostate cancer from benign prostatic hyperplasia","volume":"13","year":"2017","journal-title":"Metabolomics"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1186\/s13395-018-0188-4","article-title":"Metabolic derangements of skeletal muscle from a murine model of glioma cachexia","volume":"9","author":"Cui","year":"2019","journal-title":"Skelet. Muscle"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"145","DOI":"10.1007\/s13539-012-0101-7","article-title":"Metabolic derangements in the gastrocnemius and the effect of Compound A therapy in a murine model of cancer cachexia","volume":"4","author":"Wysong","year":"2013","journal-title":"J. Cachexia. Sarcopenia Muscle"},{"key":"ref_37","doi-asserted-by":"crossref","unstructured":"Migliavacca, E., Tay, S.K.H., Patel, H.P., Sonntag, T., Civiletto, G., McFarlane, C., Forrester, T., Barton, S.J., Leow, M.K., and Antoun, E. (2019). Mitochondrial oxidative capacity and NAD+ biosynthesis are reduced in human sarcopenia across ethnicities. Nat. Commun., 10.","DOI":"10.1038\/s41467-019-13694-1"},{"key":"ref_38","first-page":"247","article-title":"Dose-dependent effects of leucine supplementation on preservation of muscle mass in cancer cachectic mice","volume":"26","author":"Peters","year":"2011","journal-title":"Oncol. Rep."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"435","DOI":"10.1080\/13547500802012858","article-title":"Metabonomics in cancer diagnosis: Mass spectrometry-based profiling of urinary nucleosides from breast cancer patients","volume":"13","author":"Frickenschimidt","year":"2008","journal-title":"Biomarkers"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"57","DOI":"10.1016\/j.cca.2013.10.008","article-title":"Urinary cytidine as an adjunct biomarker to improve the diagnostic ratio for gastric cancer in Taiwanese patients","volume":"428","author":"Lo","year":"2014","journal-title":"Clin. Chim. Acta"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1007\/s00726-009-0269-0","article-title":"Amino acids: Metabolism, functions, and nutrition","volume":"37","author":"Wu","year":"2009","journal-title":"Amino Acids"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"140","DOI":"10.1002\/jcsm.12360","article-title":"Cachexia induced by cancer and chemotherapy yield distinct perturbations to energy metabolism","volume":"10","author":"Pin","year":"2019","journal-title":"J. Cachexia. Sarcopenia Muscle"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"216","DOI":"10.1007\/s11306-008-0113-7","article-title":"Metabolomic analysis of cancer cachexia reveals distinct lipid and glucose alterations","volume":"4","author":"Ardeshirpour","year":"2008","journal-title":"Metabolomics"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"730","DOI":"10.1007\/s11306-012-0485-6","article-title":"Cancer cachexia\u2019s metabolic signature in a murine model confirms a distinct entity","volume":"9","author":"Asher","year":"2013","journal-title":"Metabolomics"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"348","DOI":"10.1002\/jcsm.12270","article-title":"Multiplatform plasma fingerprinting in cancer cachexia: A pilot observational and translational study","volume":"9","author":"Cala","year":"2018","journal-title":"J. Cachexia Sarcopenia Muscle"}],"container-title":["Nutrients"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2072-6643\/12\/7\/2106\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T09:49:00Z","timestamp":1760176140000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2072-6643\/12\/7\/2106"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,7,16]]},"references-count":45,"journal-issue":{"issue":"7","published-online":{"date-parts":[[2020,7]]}},"alternative-id":["nu12072106"],"URL":"https:\/\/doi.org\/10.3390\/nu12072106","relation":{},"ISSN":["2072-6643"],"issn-type":[{"value":"2072-6643","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,7,16]]}}}