Professor Antonio Vidal-Puig

英国医学科学院院士、英国皇家医学院院士、剑桥大学教授、苏州大学名誉/讲座教授

Fellow of Academy of Medical Science, UK

Fellow of Royal College of Physician, London, UK

Professor of Molecular Nutrition & Metabolism

Dept of Clinical Biochemistry, University of Cambridge

Associate Director of the MRC Metabolic Diseases Unit

Honorary Professor of Soochow University

Email address:  ajv22@cam.ac.uk

https://www.mrl.ims.cam.ac.uk/staff/professor-antonio-vidal-puig

Research Interests 

Molecular Mechanisms of Energy Balance 

Our research program is dedicated to exploring mechanisms linking obesity with cardiometabolic complications. These include the molecular mechanisms that control energy expenditure, fat deposition, and the partitioning of energy towards oxidation or storage, with a particular focus on how these processes are disrupted in obesity. Our work addresses the following interrelated questions: 

Adipose Tissue Dysfunction and Lipotoxicity: We investigate how dysfunction in adipose tissue, especially in white adipose tissue (WAT), leads to lipotoxicity—a condition where ectopic fat accumulation in non-adipose tissues (like liver, muscle, and pancreas) induces cellular injury, inflammation, and insulin resistance. By examining the mechanisms that cause adipose tissue to fail in safely storing lipids, we aim to identify how this dysfunction contributes to the development of metabolic-associated steatotic liver disease (MASLD) and other complications of metabolic syndrome. 

Brown Fat Biology as an Anti-Lipotoxic Strategy: Recognising the protective role of brown adipose tissue (BAT) in energy expenditure and thermogenesis, our research explores the activation of BAT and the browning of WAT (conversion to beige adipocytes) as strategies to counteract lipotoxicity. By enhancing lipid oxidation in these thermogenic tissues, we aim to reduce ectopic fat deposition and alleviate the associated metabolic burden. Our studies focus on understanding the molecular signals that regulate BAT activity and beige adipocyte formation, with the goal of developing therapeutic interventions that leverage these pathways to prevent or reverse lipotoxicity. 

Nutrient Partitioning and Energy Metabolism: Our research also focuses on how modulating nutrient partitioning can prevent the adverse effects of excess fat storage. We investigate mechanisms that promote fatty acid oxidation in skeletal muscle and reduce lipid accumulation in adipose tissue, aiming to redirect energy utilisation in ways that support metabolic health and combat obesity. 

MASLD as a Manifestation of Lipotoxicity: MASLD represents a critical manifestation of lipotoxicity, characterised by ectopic fat deposition in the liver, which can progress to inflammation, fibrosis, and further complications. Our framework integrates the study of how cellular injury, inflammation, and fibrosis are coupled in the context of lipotoxicity. By dissecting these pathways, we hope to elucidate the links between adipose tissue dysfunction, systemic metabolic disturbances, and organ-specific pathologies like MASLD. 

To address these complex challenges, our laboratory employs an Integrated Physiology approach, utilising genetically modified models to unravel the intricacies of energy homeostasis. We complement this with Systems Biology methods, including transcriptomic, lipidomic, and bioinformatic analyses, to map lipid metabolic networks across different organs and understand their relevance to insulin resistance and metabolic disease. Our ultimate goal is to identify novel biomarkers and therapeutic targets that can inform precision medicine approaches for treating obesity and its associated metabolic disorders. 

Key publications:

1. Luka Gebel, Chander Velu & Antonio Vidal-Puig. The strategy behind one of the most successful labs in the world (2024) Nature 2024 Jun;630(8018):813-816. doi: 10.1038/d41586-024-02085- 

2. I Kamzolas, M Vacca, L Mørch Harder, S Rodriguez-Cuenca, L Tiniakos, ... A Vidal-Puig. An unbiased ranking of murine dietary models based on their proximity to human Metabolic Dysfunction–associated Steatotic Liver Disease (MASLD). Nat Metab. 2024 Jun 12. doi: 10.1038/s42255-024-01043-6. PMID: 38867022 

3. Tan J, Virtue S, Norris DM, Conway OJ, Yang M, Bidault G, Gribben C, Lugtu F, Kamzolas I, Krycer JR, Mills RJ, Liang L, Pereira C, Dale M, Shun-Shion AS, Baird HJ, Horscroft JA, Sowton AP, Ma M, Carobbio S, Petsalaki E, Murray AJ, Gershlick DC, Nathan JA, Hudson JE, Vallier L, Fisher-Wellman KH, Frezza C, Vidal-Puig A*, Fazakerley DJ. Limited oxygen in standard cell culture alters the metabolism and function of differentiated cells. EMBO J. 2024 Apr 5. doi: 10.1038/s44318-024-00084-7. PMID: 38580776 

4. Pellegrinelli V, Rodriguez-Cuenca S, Rouault C, Figueroa-Juarez E, Schilbert H, Virtue S, Moreno-Navarrete JM, Bidault G, Vázquez-Borrego MC, Dias AR, Pucker B, Dale M, Campbell M, Carobbio S, Lin YH, Vacca M, Aron-Wisnewsky J, Mora S, Masiero MM, Emmanouilidou A, Mukhopadhyay S, Dougan G, den Hoed M, Loos RJF, Fernández-Real JM, Chiarugi D, Clément K, Vidal-Puig A. Dysregulation of macrophage PEPD in obesity determines adipose tissue fibro-inflammation and insulin resistance. Nat Metab. 2022 Apr;4(4):476-494. Doi: 10.1038/s42255-022-00561-5. Epub 2022 Apr 25. PMID: 35478031 

5.Guillaume Bidault, Samuel Virtue, Kasparas Petkevicius, Helen E. Jolin, Aurélien Dugourd, Anne-Claire Guénantin, Jennifer Leggat, Betania Mahler-Araujo, Brian Y. H. Lam, Marcella K. Ma, Martin Dale, Stefania Carobbio, Arthur Kaser, Padraic G. Fallon, Julio Saez-Rodriguez, Andrew N. J. McKenzie & Antonio Vidal-Puig. SREBP1-induced fatty acid synthesis depletes macrophages antioxidant defences to promote their alternative activation. Nature Metabolism volume 3, pages1150–1162 (2021)C. PMID: 34531575 PMCID: PMCID:7611716 

Johnson K, Leary PJ, Govaere O, Barter MJ, Charlton SH, Cockell SJ, Tiniakos D, Zatorska M, Bedossa P, Brosnan MJ, Cobbold JF, Ekstedt M, Aithal GP, Clément K, Schattenberg JM, Boursier J, Ratziu V, Bugianesi E, Anstee QM, Daly AK; LITMUS Consortium Investigators. Increased serum miR-193a-5p during non-alcoholic fatty liver disease progression: Diagnostic and mechanistic relevance. JHEP Rep. 2021 Nov 25;4(2):100409.  Doi: 10.1016/j.jhepr.2021.100409. PMID: 35072021 PMCID: PMC8762473