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.

1. 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).
2. Whether modifications in adipogenesis and remodeling of adipose tissue may be good strategies to ameliorate the metabolic effects associated with obesity.
3. The molecular mechanisms that control energy expenditure and brown fat activation.
4. 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

Lopez M, Varela L, Vazquez MJ, Rodriguez-Cuenca S, Gonzalez CR, Velagapudi VR, Morgan DA, Schoenmakers E, Agassandian K, Lage R, de Morentin PB, Tovar S, Nogueiras R, Carling D, Lelliott C, Gallego R, Oresic M, Chatterjee K, Saha AK, Rahmoundi K, Dieguez C, Vidal-Puig A. (2010). Hypothalamic AMPK and fatty acid metabolism mediate thyroid regulation of energy balance. Nat Med, 16(9):1001-8. PMID: 20802499. PMCID: PMC2935934.

Hagen RM, Rodriguez-Cuenca S, Vidal-Puig A. (2010). An allostatic control of membrane lipid composition by SREBP1. FEBS Lett, 584(12):2689-98. PMID: 20385130.

Ishii KA, Fumoto T, Iwai K, Takeshita S, Ito M, Shimohata N, Aburatani H, Taketani S, Lelliott CJ, Vidal-Puig A, Ikeda K. (2009). Coordination of PGC-1beta and iron uptake in mitochondrial biogenesis and osteoclast activation. Nat Med, 15(3):259-66. PMID: 19252502.

Lagathu C, Christodoulides C, Virtue S, Cawthorn WP, Franzin C, Kimber WA, Nora ED, Campbell M, Medina-Gomez G, Cheyette BN, Vidal-Puig AJ, Sethi JK. (2009). Dact1, a nutritionally regulated preadipocyte gene, controls adipogenesis by coordinating the Wnt/beta-catenin signaling network. Diabetes, 58(3):609-19. PMID: 19073771. PMCID: PMC2646059.

Oresic M, Hänninen VA, Vidal-Puig A. (2008). Lipidomics: a new window to biomedical frontiers. Trends Biotechnol, 26(12):647-52. PMID: 18951641.

Virtue S, Vidal-Puig A. (2008). It’s not how fat you are, it’s what you do with it that counts. PLoS Biol, 6(9):e237. PMID: 18816166. PMCID: PMC2553843.

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. (2008). Hypothalamic fatty acid metabolism mediates the orexigenic action of ghrelin. Cell Metab, 7(5):389-99. PMID: 18460330.

Yetukuri L, Ekroos K, Vidal-Puig A, Oresic M. (2008). Informatics and computational strategies for the study of lipids. Mol Biosyst, 4(2):121-7. PMID: 18213405.

Chakravarthy MV, Zhu Y, López M, Yin L, Wozniak DF, Coleman T, Hu Z, Wolfgang M, Vidal-Puig A, Lane MD, Semenkovich CF. (2007). Brain fatty acid synthase activates PPARalpha to maintain energy homeostasis. J Clin Invest, 117(9):2539-52. PMID: 17694178. PMCID: PMC1937501.

Medina-Gomez G, Gray SL, Yetukuri L, Shimomura K, Virtue S, Campbell M, Curtis RK, Jimenez-Linan M, Blount M, Yeo GS, Lopez M, Seppänen-Laakso T, Ashcroft FM, Oresic M, Vidal-Puig A. (2007). PPAR gamma 2 prevents lipotoxicity by controlling adipose tissue expandability and peripheral lipid metabolism. PLoS Genet, 3(4):e64. PMID: 17465682. PMCID: PMC1857730.

Yetukuri L, Katajamaa M, Medina-Gomez G, Seppänen-Laakso T, Vidal-Puig A, Oresic M. (2007). Bioinformatics strategies for lipidomics analysis: characterization of obesity related hepatic steatosis. BMC Syst Biol, 1:12. PMID: 17408502. PMCID: PMC1839890.

Lelliott CJ, Medina-Gomez G, Petrovic N, Kis A, Feldmann HM, Bjursell M, Parker N, Curtis K, Campbell M, Hu P, Zhang D, Litwin SE, Zaha VG, Fountain KT, Boudina S, Jimenez-Linan M, Blount M, Lopez M, Meirhaeghe A, Bohlooly YM, Storlien L, Stromstedt M, Snaith M, Oresic M, Abel ED, Cannon B, Vidal-Puig A. (2006). Ablation of PGC-1beta results in defective mitochondrial activity, thermogenesis, hepatic function, and cardiac performance. PLoS Biol, 4(11):e369. PMID: 17090215. PMCID: PMC1634886.

Gray SL, Nora ED, Grosse J, Manieri M, Stoeger T, Medina-Gomez G, Burling K, Wattler S, Russ A, Yeo GS, Chatterjee VK, O’Rahilly S, Voshol PJ, Cinti S, Vidal-Puig A. (2006). Leptin deficiency unmasks the deleterious effects of impaired peroxisome proliferator-activated receptor gamma function (P465L PPARgamma) in mice. Diabetes, 55(10):2669-77, 2006. PMID: 17003330.

Lopez M, Lelliott CJ, Tovar S, Kimber W, Gallego R, Virtue S, Blount M, Vazquez MJ, Finer N, Powles TJ, O’Rahilly S, Saha AK, Dieguez C, Vidal-Puig AJ. (2006). Tamoxifen-induced anorexia is associated with fatty acid synthase inhibition in the ventromedial nucleus of the hypothalamus and accumulation of malonyl-CoA. Diabetes, 55(5):1327-36. PMID: 16644689.

Christodoulides C, Laudes M, Cawthorn WP, Schinner S, Soos M, O’Rahilly S, Sethi JK, Vidal-Puig A. (2006). The Wnt antagonist Dickkopf-1 and its receptors are coordinately regulated during early human adipogenesis. J Cell Sci, 119(Pt 12):2613-20. PMID: 16763196.

Medina-Gomez, G; Virtue S; Leliott C, Boiani R Christodoulides C; Campbell M, Curtis K, Yeo G, Jimenez-Linan,M; Blount M; Seppänen-Laakso, T; Sethi J, O’Rahilly S, Cinti S, Brindle K, Oresic M, Burcelin R, Vidal-Puig A. (2005). The link between nutritional status and insulin sensitivity is dependent on the adipocyte-specific peroxisome proliferator-activated receptor-gamma2 isoform. Diabetes, 54(6):1706-16. PMID: 15919792.