Molecular Mechanisms of Energy Balance
Our program of research explores the molecular mechanisms involved in controlling energy expenditure, fat deposition, and the mechanisms controlling the partition of energy towards oxidation or storage.
Specifically we are interested in the following interrelated questions.
- How the expansion of adipose tissue typically associated with obesity relates to the development of the Metabolic Syndrome. More specifically we are exploring whether lipotoxicity and/or changes in adipokines secreted by adipose tissue affect insulin sensitivity in other organs (skeletal muscle, heart, liver, brain, beta cells and macrophages).
- Whether modifications in adipogenesis and remodeling of adipose tissue may be good strategies to ameliorate the metabolic effects associated with obesity.
- The molecular mechanisms that control energy expenditure and brown fat activation.
- Whether modulation of partitioning of nutrients towards fatty acid oxidation in skeletal muscle and away from storage in adipose tissue may prevent the devastating metabolic effects of obesity.
To address these challenges is a daunting task that requires the modulation of highly integrated and complex mechanisms of energy homeostasis designed to prevent negative energy balances. According to this integrated concept of energy homeostasis, my laboratory is using an Integrated Physiology approach that relies greatly upon the generation and detailed in vivo phenotyping of genetically modified organisms. Together with Systems Biology approach integrating transcriptomic and lipidomic analysis, using bioinformatics to identify organ specific lipid metabolic networks relevant for insulin resistance and metabolic disease.
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
Rao S, Yang X, Ohshiro K, Zaidi S, Wang Z, Shetty K, Xiang X, Hassan MI, Mohammad T, Latham PS, Nguyen BN, Wong L, Yu H, Al-Abed Y, Mishra B, Vacca M, Guenigault G, Allison MED, Vidal-Puig A, Benhammou JN, Alvarez M, Pajukanta P, Pisegna JR, Mishra L. β2-spectrin (SPTBN1) as a therapeutic target for diet-induced liver disease and preventing cancer development. Sci Transl Med. 2021 Dec 15;13(624):eabk2267. Doi: 10.1126/scitranslmed.abk2267. PMID: 34910547 PMCID:PMC8941321
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
Furse S, Virtue S, Snowden SG, Vidal-Puig A, Stevenson PC, Chiarugi D, Koulman A. Dietary PUFA drives various systems-level changes in lipid metabolism. Mol Metab. 2022 Feb 9;101457. Doi: 10.1016/j.molmet.2022.101457. PMID: 35150907 PMCID: PMC8894240
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