Periodic dietary restriction of animal products induces metabolic reprogramming in humans with effects on cardiometabolic health
Abstract Dietary interventions constitute powerful approaches for disease prevention and treatment. However, the molecular mechanisms through which diet affects health remain underexplored in humans. Here, we compare plasma metabolomic and proteomic profiles between dietary states for a unique group...
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| Format: | Article |
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Nature Portfolio
2025-04-01
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| Series: | npj Metabolic Health and Disease |
| Online Access: | https://doi.org/10.1038/s44324-025-00057-2 |
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| author | Konstantinos Rouskas Ozvan Bocher Alexandros Simistiras Christina Emmanouil Panagiotis Mantas Anargyros Skoulakis Young-Chan Park Alexandros Dimopoulos Stavros Glentis Gabi Kastenmüller Eleftheria Zeggini Antigone S. Dimas |
| author_facet | Konstantinos Rouskas Ozvan Bocher Alexandros Simistiras Christina Emmanouil Panagiotis Mantas Anargyros Skoulakis Young-Chan Park Alexandros Dimopoulos Stavros Glentis Gabi Kastenmüller Eleftheria Zeggini Antigone S. Dimas |
| author_sort | Konstantinos Rouskas |
| collection | DOAJ |
| description | Abstract Dietary interventions constitute powerful approaches for disease prevention and treatment. However, the molecular mechanisms through which diet affects health remain underexplored in humans. Here, we compare plasma metabolomic and proteomic profiles between dietary states for a unique group of individuals who alternate between omnivory and restriction of animal products for religious reasons. We find that short-term restriction drives reductions in levels of lipid classes and of branched-chain amino acids, not detected in a control group of individuals, and results in metabolic profiles associated with decreased risk for all-cause mortality. We show that 23% of proteins whose levels are affected by dietary restriction are druggable targets and reveal that pro-longevity hormone FGF21 and seven additional proteins (FOLR2, SUMF2, HAVCR1, PLA2G1B, OXT, SPP1, HPGDS) display the greatest magnitude of change. Through Mendelian randomization we demonstrate potentially causal effects of FGF21 and HAVCR1 on risk for type 2 diabetes, of HPGDS on BMI, and of OXT on risk for lacunar stroke. Collectively, we find that restriction-associated reprogramming improves metabolic health and emphasise high-value targets for pharmacological intervention. |
| format | Article |
| id | doaj-art-92dffe3f0c3e4af0b5697dca71417ef1 |
| institution | DOAJ |
| issn | 2948-2828 |
| language | English |
| publishDate | 2025-04-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | npj Metabolic Health and Disease |
| spelling | doaj-art-92dffe3f0c3e4af0b5697dca71417ef12025-08-20T03:10:07ZengNature Portfolionpj Metabolic Health and Disease2948-28282025-04-013111410.1038/s44324-025-00057-2Periodic dietary restriction of animal products induces metabolic reprogramming in humans with effects on cardiometabolic healthKonstantinos Rouskas0Ozvan Bocher1Alexandros Simistiras2Christina Emmanouil3Panagiotis Mantas4Anargyros Skoulakis5Young-Chan Park6Alexandros Dimopoulos7Stavros Glentis8Gabi Kastenmüller9Eleftheria Zeggini10Antigone S. Dimas11Institute for Bioinnovation, Biomedical Sciences Research Center ‘Alexander Fleming’, Fleming 34Institute of Translational Genomics, Helmholtz Zentrum München – German Research Center for Environmental HealthInstitute for Bioinnovation, Biomedical Sciences Research Center ‘Alexander Fleming’, Fleming 34Institute for Bioinnovation, Biomedical Sciences Research Center ‘Alexander Fleming’, Fleming 34Institute for Bioinnovation, Biomedical Sciences Research Center ‘Alexander Fleming’, Fleming 34Institute for Bioinnovation, Biomedical Sciences Research Center ‘Alexander Fleming’, Fleming 34Institute of Translational Genomics, Helmholtz Zentrum München – German Research Center for Environmental HealthInstitute for Bioinnovation, Biomedical Sciences Research Center ‘Alexander Fleming’, Fleming 34Institute for Bioinnovation, Biomedical Sciences Research Center ‘Alexander Fleming’, Fleming 34Institute of Computational Biology, Helmholtz Zentrum München – German Research Center for Environmental HealthInstitute of Translational Genomics, Helmholtz Zentrum München – German Research Center for Environmental HealthInstitute for Bioinnovation, Biomedical Sciences Research Center ‘Alexander Fleming’, Fleming 34Abstract Dietary interventions constitute powerful approaches for disease prevention and treatment. However, the molecular mechanisms through which diet affects health remain underexplored in humans. Here, we compare plasma metabolomic and proteomic profiles between dietary states for a unique group of individuals who alternate between omnivory and restriction of animal products for religious reasons. We find that short-term restriction drives reductions in levels of lipid classes and of branched-chain amino acids, not detected in a control group of individuals, and results in metabolic profiles associated with decreased risk for all-cause mortality. We show that 23% of proteins whose levels are affected by dietary restriction are druggable targets and reveal that pro-longevity hormone FGF21 and seven additional proteins (FOLR2, SUMF2, HAVCR1, PLA2G1B, OXT, SPP1, HPGDS) display the greatest magnitude of change. Through Mendelian randomization we demonstrate potentially causal effects of FGF21 and HAVCR1 on risk for type 2 diabetes, of HPGDS on BMI, and of OXT on risk for lacunar stroke. Collectively, we find that restriction-associated reprogramming improves metabolic health and emphasise high-value targets for pharmacological intervention.https://doi.org/10.1038/s44324-025-00057-2 |
| spellingShingle | Konstantinos Rouskas Ozvan Bocher Alexandros Simistiras Christina Emmanouil Panagiotis Mantas Anargyros Skoulakis Young-Chan Park Alexandros Dimopoulos Stavros Glentis Gabi Kastenmüller Eleftheria Zeggini Antigone S. Dimas Periodic dietary restriction of animal products induces metabolic reprogramming in humans with effects on cardiometabolic health npj Metabolic Health and Disease |
| title | Periodic dietary restriction of animal products induces metabolic reprogramming in humans with effects on cardiometabolic health |
| title_full | Periodic dietary restriction of animal products induces metabolic reprogramming in humans with effects on cardiometabolic health |
| title_fullStr | Periodic dietary restriction of animal products induces metabolic reprogramming in humans with effects on cardiometabolic health |
| title_full_unstemmed | Periodic dietary restriction of animal products induces metabolic reprogramming in humans with effects on cardiometabolic health |
| title_short | Periodic dietary restriction of animal products induces metabolic reprogramming in humans with effects on cardiometabolic health |
| title_sort | periodic dietary restriction of animal products induces metabolic reprogramming in humans with effects on cardiometabolic health |
| url | https://doi.org/10.1038/s44324-025-00057-2 |
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