{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,27]],"date-time":"2026-07-27T10:35:15Z","timestamp":1785148515612,"version":"3.55.0"},"reference-count":25,"publisher":"MDPI AG","issue":"5","license":[{"start":{"date-parts":[[2021,4,29]],"date-time":"2021-04-29T00:00:00Z","timestamp":1619654400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Nutrients"],"abstract":"<jats:p>Fibroblast growth factor 21 (FGF21) is a human metabolic hormone whose effects include modification of macronutrient preference and energy homeostasis. In animal models, FGF21 has been shown to have beneficial effects on cardiometabolic outcomes, Alzheimer\u2019s disease risk and lifespan. In this study, the single-nucleotide polymorphism rs838133 in the FGF21 gene region was leveraged to investigate the potential clinical effects of targeting FGF21. The FGF21 G allele was associated with lower intakes of total sugars and alcohol, and higher intakes of protein and fat as well as favourable with lipid levels, blood pressure traits, waist-to-hip ratio, systemic inflammation, cardiovascular outcomes, Alzheimer\u2019s disease risk and lifespan. These findings may be used to anticipate the effects of pharmacologically increasing FGF21 signalling.<\/jats:p>","DOI":"10.3390\/nu13051504","type":"journal-article","created":{"date-parts":[[2021,4,29]],"date-time":"2021-04-29T10:30:41Z","timestamp":1619692241000},"page":"1504","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":16,"title":["Genetic Evidence Supporting Fibroblast Growth Factor 21 Signalling as a Pharmacological Target for Cardiometabolic Outcomes and Alzheimer\u2019s Disease"],"prefix":"10.3390","volume":"13","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0118-0341","authenticated-orcid":false,"given":"Susanna C.","family":"Larsson","sequence":"first","affiliation":[{"name":"Department of Surgical Sciences, Uppsala University, 751 85 Uppsala, Sweden"},{"name":"Unit of Cardiovascular and Nutritional Epidemiology, Institute of Environmental Medicine, Karolinska Institutet, 171 77 Stockholm, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7312-7078","authenticated-orcid":false,"given":"Dipender","family":"Gill","sequence":"additional","affiliation":[{"name":"Department of Epidemiology and Biostatistics, School of Public Health, St. Mary\u2032s Hospital, Imperial College London, London W2 1PG, UK"},{"name":"Clinical Pharmacology and Therapeutics Section, Institute of Medical and Biomedical Education and Institute for Infection and Immunity, St. George\u2019s, University of London, London SW17 0QT, UK"},{"name":"Clinical Pharmacology Group, Pharmacy and Medicines Directorate, St. George\u2019s University Hospitals NHS Foundation Trust, London SW17 0QT, UK"},{"name":"Novo Nordisk Research Centre Oxford, Old Road Campus, Oxford OX3 7FZ, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,4,29]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"309","DOI":"10.1038\/s42255-021-00354-2","article-title":"Metabolic Messengers: FGF21","volume":"3","author":"Flippo","year":"2021","journal-title":"Nat. Metab."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"bqaa019","DOI":"10.1210\/endocr\/bqaa019","article-title":"FGF21 and the physiological regulation of macronutrient rreference","volume":"161","author":"Hill","year":"2020","journal-title":"Endocrinology"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"419","DOI":"10.3389\/fphys.2019.00419","article-title":"FGF21 as Modulator of Metabolism in Health and Disease","volume":"10","author":"Tezze","year":"2019","journal-title":"Front. Physiol."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"335","DOI":"10.1016\/j.cmet.2015.12.003","article-title":"FGF21 Mediates Endocrine Control of Simple Sugar Intake and Sweet Taste Preference by the Liver","volume":"23","author":"BonDurant","year":"2016","journal-title":"Cell Metab."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"344","DOI":"10.1016\/j.cmet.2015.12.008","article-title":"FGF21 Regulates Sweet and Alcohol Preference","volume":"23","author":"Talukdar","year":"2016","journal-title":"Cell Metab."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"19521","DOI":"10.1038\/s41598-020-76593-2","article-title":"FGF21 signaling in glutamatergic neurons is required for weight loss associated with dietary protein dilution","volume":"10","author":"Flippo","year":"2020","journal-title":"Sci. Rep."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"654","DOI":"10.1038\/s41574-020-0386-0","article-title":"The therapeutic potential of FGF21 in metabolic diseases: From bench to clinic","volume":"16","author":"Geng","year":"2020","journal-title":"Nat. Rev. Endocrinol."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"2555","DOI":"10.2174\/1381612825666190716101411","article-title":"Therapeutic Approaches to Alzheimer\u2019s Type of Dementia: A Focus on FGF21 Mediated Neuroprotection","volume":"25","author":"Taliyan","year":"2019","journal-title":"Curr. Pharm. Des."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"e00065","DOI":"10.7554\/eLife.00065","article-title":"The starvation hormone, fibroblast growth factor-21, extends lifespan in mice","volume":"1","author":"Zhang","year":"2012","journal-title":"Elife"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"327","DOI":"10.1016\/j.celrep.2018.03.070","article-title":"A common allele in FGF21 associated with sugar intake is associated with body shape, lower total body-fat percentage, and higher blood pressure","volume":"23","author":"Frayling","year":"2018","journal-title":"Cell Rep."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"551","DOI":"10.1161\/CIRCGEN.120.003061","article-title":"Use of a Genetic Variant Related to Circulating FXa (Activated Factor X) Levels to Proxy the Effect of FXa Inhibition on Cardiovascular Outcomes","volume":"13","author":"Gill","year":"2020","journal-title":"Circ. Genom. Precis. Med."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"1045","DOI":"10.1016\/j.cmet.2017.04.009","article-title":"FGF21 is a sugar-induced hormone associated with sweet intake and preference in humans","volume":"25","author":"Soberg","year":"2017","journal-title":"Cell Metab."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"659","DOI":"10.1038\/ng.2274","article-title":"A genome-wide approach accounting for body mass index identifies genetic variants influencing fasting glycemic traits and insulin resistance","volume":"44","author":"Manning","year":"2012","journal-title":"Nat. Genet."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"1274","DOI":"10.1038\/ng.2797","article-title":"Discovery and refinement of loci associated with lipid levels","volume":"45","author":"Willer","year":"2013","journal-title":"Nat. Genet."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"e34408","DOI":"10.7554\/eLife.34408","article-title":"The MR-Base platform supports systematic causal inference across the human phenome","volume":"7","author":"Hemani","year":"2018","journal-title":"Elife"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"433","DOI":"10.1161\/CIRCRESAHA.117.312086","article-title":"Identification of 64 Novel Genetic Loci Provides an Expanded View on the Genetic Architecture of Coronary Artery Disease","volume":"122","author":"Verweij","year":"2018","journal-title":"Circ. Res."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"1234","DOI":"10.1038\/s41588-018-0171-3","article-title":"Biobank-driven genomic discovery yields new insight into atrial fibrillation biology","volume":"50","author":"Nielsen","year":"2018","journal-title":"Nat. Genet."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"524","DOI":"10.1038\/s41588-018-0058-3","article-title":"Multiancestry genome-wide association study of 520,000 subjects identifies 32 loci associated with stroke and stroke subtypes","volume":"50","author":"Malik","year":"2018","journal-title":"Nat. Genet."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"1505","DOI":"10.1038\/s41588-018-0241-6","article-title":"Fine-mapping type 2 diabetes loci to single-variant resolution using high-density imputation and islet-specific epigenome maps","volume":"50","author":"Mahajan","year":"2018","journal-title":"Nat. Genet."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"166","DOI":"10.1093\/hmg\/ddy327","article-title":"Meta-analysis of genome-wide association studies for body fat distribution in 694 649 individuals of European ancestry","volume":"28","author":"Pulit","year":"2019","journal-title":"Hum. Mol. Genet."},{"key":"ref_21","unstructured":"FinnGen Consortium (2020, December 10). FinnGen Documentation of R4 Release. Available online: https:\/\/finngen.gitbook.io\/documentation\/."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"404","DOI":"10.1038\/s41588-018-0311-9","article-title":"Genome-wide meta-analysis identifies new loci and functional pathways influencing Alzheimer\u2019s disease risk","volume":"51","author":"Jansen","year":"2019","journal-title":"Nat. Genet."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"e39856","DOI":"10.7554\/eLife.39856","article-title":"Genomics of 1 million parent lifespans implicates novel pathways and common diseases and distinguishes survival chances","volume":"8","author":"Timmers","year":"2019","journal-title":"Elife"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"163","DOI":"10.1038\/s41467-019-13690-5","article-title":"Genome-wide association and Mendelian randomisation analysis provide insights into the pathogenesis of heart failure","volume":"11","author":"Shah","year":"2020","journal-title":"Nat. Commun."},{"key":"ref_25","doi-asserted-by":"crossref","unstructured":"Giambartolomei, C., Vukcevic, D., Schadt, E.E., Franke, L., Hingorani, A.D., Wallace, C., and Plagnol, V. (2014). Bayesian Test for Colocalisation between Pairs of Genetic Association Studies Using Summary Statistics. PLoS Genet., 10.","DOI":"10.1371\/journal.pgen.1004383"}],"container-title":["Nutrients"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2072-6643\/13\/5\/1504\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T05:55:28Z","timestamp":1760162128000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2072-6643\/13\/5\/1504"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,4,29]]},"references-count":25,"journal-issue":{"issue":"5","published-online":{"date-parts":[[2021,5]]}},"alternative-id":["nu13051504"],"URL":"https:\/\/doi.org\/10.3390\/nu13051504","relation":{},"ISSN":["2072-6643"],"issn-type":[{"value":"2072-6643","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,4,29]]}}}