Research Interests
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.
Selected Publications
1.Petkevicius K, Virtue S, Bidault G, Jenkins B, Çubuk C, Morgantini C, Aouadi M, Dopazo J, Serlie MJ, Koulman A, Vidal-Puig Accelerated phosphatidylcholine turnover in macrophages promotes adipose tissue inflammation in obesity.Elife. 2019 Aug 16;8. pii: e47990. doi: 10.7554/eLife.47990.PMID:31418690
2.Rana BMJ, Jou E, Barlow JL, Rodriguez-Rodriguez N, Walker JA, Knox C, Jolin HE, Hardman CS, Sivasubramaniam M, Szeto A, Cohen ES, Scott IC, Sleeman MA, Chidomere CI, Cruz Migoni S, Caamano J, Jorgensen HF, Carobbio S, Vidal-Puig A, McKenzie ANJ. A stromal cell niche sustains ILC2-mediated type-2 conditioning in adipose tissue. J Exp Med. 2019 Sep 2;216(9):1999-2009. doi: 10.1084/jem.20190689. Epub 2019 Jun 27.PMID:31248899
3.Johann K, Cremer AL, Fischer AW, Heine M, Pensado ER, Resch J, Nock S, Virtue S, Harder L, Oelkrug R, Astiz M, Brabant G, Warner A, Vidal-Puig A, Oster H, Boelen A, López M, Heeren J, Dalley JW, Backes H, Mittag J. Thyroid-Hormone-Induced Browning of White Adipose Tissue Does Not Contribute to Thermogenesis and Glucose Consumption. Cell Rep. 2019 Jun 11;27(11):3385-3400.e3. doi: 10.1016/j.celrep.2019.05.054.PMID:31189119
4.Araiz C, Yan A, Bettedi L, Samuelson I, Virtue S, McGavigan AK, Dani C, Vidal-Puig A, Foukas LC. Enhanced β-adrenergic signalling underlies an age-dependent beneficial metabolic effect of PI3K p110α inactivation in adipose tissue. Nature Communication. 2019 Apr 4;10(1):1546.doi: 10.1038/s41467-019-09514-1.PMID:3094872
5.Patel S, Alvarez-Guaita A, Melvin A, Rimmington D, Dattilo A, Miedzybrodzka EL, Cimino I, Maurin AC, Roberts GP, Meek CL, Virtue S, Sparks LM, Parsons SA, Redman LM, Bray GA, Liou AP, Woods RM, Parry SA, Jeppesen PB, Kolnes AJ, Harding HP, Ron D, Vidal-Puig A, Reimann F, Gribble FM, Hulston CJ, Farooqi IS, Fafournoux P, Smith SR, Jensen J, Breen D, Wu Z, Zhang BB, Coll AP, Savage DB, O’Rahilly S. GDF15 Provides an Endocrine Signal of Nutritional Stress in Mice and Humans. Cell Metab. 2019 Mar 5;29(3):707-718.e8. doi:10.1016/j.cmet.2018.12.016.
6.Pellegrinelli V, Peirce VI, Howard L, Virtue S, Turei D, Senzacqua M, FrontiniA , Dalley JW, AR Horton AR, Bidault G, SeveriI, Whittle A, Saez-Rodriguez J, Cinti S Davie AM and A Vidal-Puig Adipocyte secreted BMP8b mediates adrenergic-induced remodeling of the neuro-vascular network in adipose tissue. Nat Comm 2018 Nov 26;9(1):4974. doi: 10.1038/s41467-018-07453-x.
7.Virtue S, Petkevicius K, Moreno-Navarrete JM, Jenkins B, Hart D, Dale M, Koulman A, Fernández-Real JM, Vidal-Puig A. Peroxisome Proliferator-Activated Receptor γ2 Controls the Rate of Adipose Tissue Lipid Storage and Determines Metabolic Flexibility. Cell Rep. 2018 Aug 21;24(8):2005-2012.e7. doi: 10.1016/j.celrep.2018.07.063. PMID:30134163
8.Senyilmaz-Tiebe D, Pfaff DH, Virtue S, Schwarz KV, Fleming T, Altamura S, Muckenthaler MU, Okun JG, Vidal-Puig A, Nawroth P, Teleman AA. Dietary stearic acid regulates mitochondria in vivo in humans. Nat Commun. 2018 Aug 7;9(1):3129. doi: 10.1038/s41467-018-05614-6. PMID:3008734
9.Tan CY, Virtue S, Bidault G, Dale M, Hagen R, Griffin JL, Vidal-Puig A. Brown Adipose Tissue Thermogenic Capacity Is Regulated by Elovl6. Cell Rep. 2015 Dec 15;13(10):2039-47. doi: 10.1016/j.celrep.2015.11.004. Epub 2015 Nov 25
10.Whittle AJ, Jiang M, Peirce V, Relat J, Virtue S, Ebinuma H, Fukamachi I, Yamaguchi T, Takahashi M, Murano T, Tatsuno I, Takeuchi M, Nakaseko C, Jin W, Jin Z, Campbell M, Schneider WJ, Vidal-Puig A*, Bujo H*. Soluble LR11/SorLA represses thermogenesis in adipose tissue and correlates with BMI in humans. Nat Commun. 2015 Nov 20;6:8951. doi: 10.1038/ncomms9951.* Corresponding Autho
11.Senyilmaz D, Virtue S, Xu X, Tan CY, Griffin JL, Miller AK, Vidal-Puig A, Teleman AA. Regulation of mitochondrial morphology and function by stearoylation of TFR1. 2015 Jul 27. doi: 10.1038/nature14601.
12.Barbarroja N, Rodriguez-Cuenca S, Nygren H, Camargo A, Pirraco A, Relat J, Cuadrado I, Pellegrinelli V, Medina-Gomez G, Lopez-Pedrera C, Tinahones FJ, Symons JD, Summers SA, Oresic M, Vidal-Puig A. Increased dihydroceramide/ceramide ratio mediated by defective expression of degs1 impairs adipocyte differentiation and function. 2014 Oct 28. pii: DB_140359.
13.Carobbio S, Hagen RM, Lelliott CJ, Slawik M, Medina-Gomez G, Tan CY, Sicard A, Atherton HJ, Barbarroja N, Bjursell M, Bohlooly-Y M, Virtue S, Tuthill A, Lefai E, Laville M, Wu T, Considine RV, Vidal H, Langin D, Oresic M, Tinahones FJ, Fernandez-Real JM, Griffin JL, Sethi JK, López M, Vidal-Puig A. Adaptive changes of the Insig1/SREBP1/SCD1 set point help adipose tissue to cope with increased storage demands of obesity. Diabetes 2013 Aug 6. [Epub ahead of print
14.Virtue S, Even P, Vidal-Puig A. Below Thermoneutrality, Changes in Activity Do Not Drive Changes in Total Daily Energy Expenditure between Groups of Mice. Cell Metab Nov 7;16(5):665-71 (2012
15.Ishii KA, Fumoto T, Iwai K, Takeshita S, Ito M, Shimohata N, Aburatani H, Taketani S, Lelliott CJ, Vidal-Puig A, Ikeda K. Coordination of PGC-1beta and iron uptake in mitochondrial biogenesis and osteoclast activation. Nat Med. 2009 Mar;15(3):259-66. Epub Mar 2009
16.Lopez M, Varela L, Vázquez MJ, Rodríguez-Cuenca S, González R, Velagapudi VR, Morgan DA, Schoenmakers E, Chatterjee K, Saha AK, Rahmouni K, Diéguez C, Vidal-Puig A. Hypothalamic AMPK and fatty acid metabolism mediate thyroid regulation of energy balance. Nat Med. 2010 Sep;16(9):1001-88.
17.López M, Lage R, Saha AK, Pérez-Tilve D, Vázquez MJ, Varela L, Sangiao-Alvarellos S, Tovar S, Raghay K, Rodríguez-Cuenca S, Deoliveira RM, Castañeda T, Datta R, Dong JZ, Culler M, Sleeman MW, Alvarez CV, Gallego R, Lelliott CJ, Carling D, Tschöp MH, Diéguez C, Vidal-Puig A. Hypothalamic Fatty Acid Metabolism Mediates the Orexigenic Action of Ghrelin. Cell Metab. 7;7(5):389-399. May 2008
