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Cambridge Cardiovascular



Molecular Mechanisms of Energy Balance

My team 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. This is used 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.


Key publications: 

Meal rich in carbohydrate, but not protein or fat, reveals adverse immunometabolic responses associated with obesity. Parvaresh Rizi E, Baig S, Shabeer M, Teo Y, Mok SF, Loh TP, Magkos F, Virtue S, Vidal-Puig A, Tai ES, Khoo CM, Toh SA. Nutr J. 2016 Dec 1;15(1):100.

Lipid zonation and phospholipid remodeling in nonalcoholic fatty liver disease. Hall Z, Bond NJ, Ashmore T, Sanders F, Ament Z, Wang X, Murray AJ, Bellafante E, Virtue S, Vidal-Puig A, Allison M, Davies SE, Koulman A, Vacca M, Griffin JL. Hepatology. 2016 Nov 18.

Metabolic gene expression profile in circulating mononuclear cells reflects obesity-associated metabolic inflexibility. Baig S, Parvaresh Rizi E, Shabeer M, Chhay V, Mok SF, Loh TP, Magkos F, Vidal-Puig A, Tai ES, Khoo CM, Toh SA. Nutr Metab (Lond). 2016 Oct 27;13:74.

Stearoyl-CoA Desaturase 1 Is a Key Determinant of Membrane Lipid Composition in 3T3-L1 Adipocytes. Rodriguez-Cuenca S, Whyte L, Hagen R, Vidal-Puig A, Fuller M. PLoS One. 2016 Sep 15;11(9):e0162047.

Assessment of plasma acylcarnitines before and after weight loss in obese subjects. Schooneman MG, Napolitano A, Houten SM, Ambler GK, Murgatroyd PR, Miller SR, Hollak CE, Tan CY, Virtue S, Vidal-Puig A, Nunez DJ, Soeters MR. Arch Biochem Biophys. 2016 Sep 15;606:73-80.

Genetic identification of thiosulfate sulfurtransferase as an adipocyte-expressed antidiabetic target in mice selected for leanness. Morton NM, Beltram J, Carter RN, Michailidou Z, Gorjanc G, McFadden C, Barrios-Llerena ME, Rodriguez-Cuenca S, Gibbins MT, Aird RE, Moreno-Navarrete JM, Munger SC, Svenson KL, Gastaldello A, Ramage L, Naredo G, Zeyda M, Wang ZV, Howie AF, Saari A, Sipilä P, Stulnig TM, Gudnason V, Kenyon CJ, Seckl JR, Walker BR, Webster SP, Dunbar DR, Churchill GA, Vidal-Puig A, Fernandez-Real JM, Emilsson V, Horvat S. Nat Med. 2016 Jul;22(7):771-9.

Cdkn1c Boosts the Development of Brown Adipose Tissue in a Murine Model of Silver Russell Syndrome. Van De Pette M, Tunster SJ, McNamara GI, Shelkovnikova T, Millership S, Benson L, Peirson S, Christian M, Vidal-Puig A, John RM. PLoS Genet. 2016 Mar 10;12(3):e1005916.

Chronic subordination stress selectively downregulates the insulin signaling pathway in liver and skeletal muscle but not in adipose tissue of male mice. Sanghez V, Cubuk C, Sebastián-Leon P, Carobbio S, Dopazo J, Vidal-Puig A, Bartolomucci A. Stress. 2016;19(2):214-24.

Mild cold effects on hunger, food intake, satiety and skin temperature in humans. Langeveld M, Tan CY, Soeters MR, Virtue S, Ambler GK, Watson LP, Murgatroyd PR, Chatterjee VK, Vidal-Puig A. Endocr Connect. 2016 Mar;5(2):65-73.

Mitochondria are required for pro-ageing features of the senescent phenotype. Correia-Melo C, Marques FD, Anderson R, Hewitt G, Hewitt R, Cole J, Carroll BM, Miwa S, Birch J, Merz A, Rushton MD, Charles M, Jurk D, Tait SW, Czapiewski R, Greaves L, Nelson G, Bohlooly-Y M, Rodriguez-Cuenca S, Vidal-Puig A, Mann D, Saretzki G, Quarato G, Green DR, Adams PD, von Zglinicki T, Korolchuk VI, Passos JF. EMBO J. 2016 Apr 1;35(7):724-42.

Stress-induced activation of brown adipose tissue prevents obesity in conditions of low adaptive thermogenesis. Razzoli M, Frontini A, Gurney A, Mondini E, Cubuk C, Katz LS, Cero C, Bolan PJ, Dopazo J, Vidal-Puig A, Cinti S, Bartolomucci A. Mol Metab. 2015 Nov 11;5(1):19-33.

Adipose tissue fatty acid chain length and mono-unsaturation increases with obesity and insulin resistance. Yew Tan C, Virtue S, Murfitt S, Roberts LD, Phua YH, Dale M, Griffin JL, Tinahones F, Scherer PE, Vidal-Puig A. Sci Rep. 2015 Dec 17;5:18366.

Brown Adipose Tissue Thermogenic Capacity Is Regulated by Elovl6. Tan CY, Virtue S, Bidault G, Dale M, Hagen R, Griffin JL, Vidal-Puig A. Cell Rep. 2015 Dec 15;13(10):2039-47.

Unsuppressed lipolysis in adipocytes is linked with enhanced gluconeogenesis and altered bile acid physiology in Insr(P1195L/+) mice fed high-fat-diet. Lee EY, Sakurai K, Zhang X, Toda C, Tanaka T, Jiang M, Shirasawa T, Tachibana K, Yokote K, Vidal-Puig A, Minokoshi Y, Miki T. Sci Rep. 2015 Nov 30;5:17565.

Soluble LR11/SorLA represses thermogenesis in adipose tissue and correlates with BMI in humans. 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. Nat Commun. 2015 Nov 20;6:8951.

Hypophagia and metabolic adaptations in mice with defective ATGL-mediated lipolysis cause resistance to HFD-induced obesity. Schreiber R, Hofer P, Taschler U, Voshol PJ, Rechberger GN, Kotzbeck P, Jaeger D, Preiss-Landl K, Lord CC, Brown JM, Haemmerle G, Zimmermann R, Vidal-Puig A, Zechner R. Proc Natl Acad Sci U S A. 2015 Nov 10;112(45):13850-5.

Regulation of mitochondrial morphology and function by stearoylation of TFR1. Senyilmaz D, Virtue S, Xu X, Tan CY, Griffin JL, Miller AK, Vidal-Puig A, Teleman AA. Nature. 2015 Sep 3;525(7567):124-8.

Lipopolysaccharide binding protein is an adipokine involved in the resilience of the mouse adipocyte to inflammation. Moreno-Navarrete JM, Escoté X, Ortega F, Camps M, Ricart W, Zorzano A, Vendrell J, Vidal-Puig A, Fernández-Real JM. Diabetologia. 2015 Oct;58(10):2424-34.

Ribosomal S6K1 in POMC and AgRP Neurons Regulates Glucose Homeostasis but Not Feeding Behavior in Mice. Smith MA, Katsouri L, Irvine EE, Hankir MK, Pedroni SM, Voshol PJ, Gordon MW, Choudhury AI, Woods A, Vidal-Puig A, Carling D, Withers DJ. Cell Rep. 2015 Apr 21;11(3):335-43.

Prostaglandin profiling reveals a role for haematopoietic prostaglandin D synthase in adipose tissue macrophage polarisation in mice and humans. Virtue S, Masoodi M, de Weijer BA, van Eijk M, Mok CY, Eiden M, Dale M, Pirraco A, Serlie MJ, Griffin JL, Vidal-Puig A. Int J Obes (Lond). 2015 Jul;39(7):1151-60.

Human Adipocytes Induce Inflammation and Atrophy in Muscle Cells During Obesity. Pellegrinelli V, Rouault C, Rodriguez-Cuenca S, Albert V, Edom-Vovard F, Vidal-Puig A, Clément K, Butler-Browne GS, Lacasa D. Diabetes. 2015 Sep;64(9):3121-34.

Hematopoietic IKBKE limits the chronicity of inflammasome priming and metaflammation. Patel MN, Bernard WG, Milev NB, Cawthorn WP, Figg N, Hart D, Prieur X, Virtue S, Hegyi K, Bonnafous S, Bailly-Maitre B, Chu Y, Griffin JL, Mallat Z, Considine RV, Tran A, Gual P, Takeuchi O, Akira S, Vidal-Puig A, Bennett MR, Sethi JK. Proc Natl Acad Sci U S A. 2015 Jan 13;112(2):506-11.

Increased dihydroceramide/ceramide ratio mediated by defective expression of degs1 impairs adipocyte differentiation and function. 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. Diabetes. 2014 Oct 28.

DLK1/PREF1 regulates nutrient metabolism and protects from steatosis. Charalambous M, Da Rocha ST, Radford EJ, Medina-Gomez G, Curran S, Pinnock SB, Ferrón SR, Vidal-Puig A, Ferguson-Smith AC. Proc Natl Acad Sci U S A. 2014 Nov 11;111(45):16088-93.

Understanding disease mechanisms with models of signaling pathway activities. Sebastian-Leon P, Vidal E, Minguez P, Conesa A, Tarazona S, Amadoz A, Armero C, Salavert F, Vidal-Puig A, Montaner D, Dopazo J. BMC Syst Biol. 2014 Oct 25;8(1):121.

Dihydroceramide desaturase 1, the gatekeeper of ceramide induced lipotoxicity. Rodriguez-Cuenca S, Barbarroja N, Vidal-Puig A. Biochim Biophys Acta. 2015 Jan;1851(1):40-50.

The different shades of fat. Peirce V, Carobbio S, Vidal-Puig A. Nature. 2014 Jun 5;510(7503):76-83.

Regulation of glucose homoeostasis by brown adipose tissue. Peirce V, Vidal-Puig A. Lancet Diabetes Endocrinol. 2013 Dec;1(4):353-60.

Methods for performing lipidomics in white adipose tissue. Roberts LD, West JA, Vidal-Puig A, Griffin JL. Methods Enzymol. 2014;538:211-31.

Full list of publications can be found on PubMed.

Professor of Molecular Nutrition and Metabolism
Director of Cardiometabolic Programme at the Heart and Lung Research Institute
Deputy Director of the Wellcome Trust-MRC Institute of Metabolic Science
Honorary Consultant in Metabolic Medicine at Addenbrooke’s Hospital