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.
Bidault G, Virtue S, Petkevicius K, Jolin HE, Dugourd A, Guénantin AC, Leggat J, Mahler-Araujo B, Lam BYH, Ma MK, Dale M, Carobbio S, Kaser A, Fallon PG, Saez-Rodriguez J, McKenzie ANJ, Vidal-Puig A. SREBP1-induced fatty acid synthesis depletes macrophages antioxidant defences to promote their alternative activation. Nat Metab. 2021 Sep;3(9):1150-1162. doi: 10.1038/s42255-021-00440-5. PMID: 34531575 PMCID:PMC7611716
Rodriguez-Cuenca S, Lelliot CJ, Campbell M, Peddinti G, Martinez-Uña M, Ingvorsen C, Dias AR, Relat J, Mora S, Hyötyläinen T, Zorzano A, Orešič M, Bjursell M, Bohlooly-Y M, Lindén D, Vidal-Puig A. Allostatic hypermetabolic response in PGC1α/β heterozygote mouse despite mitochondrial defects. FASEB J. 2021 Sep;35(9):e21752. doi: 10.1096/fj.202100262RR. PMID: 34369602
Furse S, Williams HEL, Watkins AJ, Virtue S, Vidal-Puig A, Amarsi R, Charalambous M, Koulman A. A pipeline for making 31 P NMR accessible for small- and large-scale lipidomics studies. Anal Bioanal Chem. 2021 Aug;413(19):4763-4773. doi: 10.1007/s00216-021-03430-4. PMID:34254158 PMCID:PMC8318958
Petkevicius K, Bidault G, Virtue S, Newland SA, Dale M, Dugourd A, Saez-Rodriguez J, Mallat Z, Vidal-Puig A. Macrophage beta2-adrenergic receptor is dispensable for the adipose tissue inflammation and function. Mol Metab. 2021 Jun;48:101220. doi: 10.1016/j.molmet.2021.101220. PMID:33774223 PMCID:PMC8086137
Carobbio S, Guenantin AC, Bahri M, Rodriguez-Fdez S, Honig F, Kamzolas I, Samuelson I, Long K, Awad S, Lukovic D, Erceg S, Bassett A, Mendjan S, Vallier L, Rosen BS, Chiarugi D, Vidal-Puig A. Unravelling the Developmental Roadmap toward Human Brown Adipose Tissue. Stem Cell Reports. 2021 Apr 13;16(4):1010. doi: 10.1016/j.stemcr.2021.03.009. PMID: 33852883 PMCID:PMC8072174