Domaine de recherche
Obésité, adipogenèse, complications métaboliques liées au surplus de poids, signalisation cellulaire, cancer.
Description des travaux
L'obésité et le cancer affectent la vie de millions de personnes. La progression de ces maladies a un impact socio-économique important. Des études menées ces dernières années montrent que l'obésité et le cancer partagent certaines similitudes relativement aux mécanismes impliqués dans leur développement. Le programme de recherche du laboratoire s'intéresse aux signaux cellulaires communs impliqués dans le développement de ces pathologies. Les travaux de mon laboratoire se répartissent dans des thèmes distincts.
Thématique obésité
L'obésité est un facteur de risque important pour le développement de la résistance à l'insuline, du diabète de type 2, de la stéatose hépatique et des maladies cardiovasculaires. Nous sommes intéressés à comprendre comment l'obésité affecte le métabolisme des tissus périphériques et comment ces tissus communiquent entre eux lors de ces dérèglements.
Thématique adipogenèse
Le développement de la cellule adipeuse est un processus complexe qui n'est pas encore parfaitement défini. Les facteurs qui indiquent aux cellules souches de s'orienter vers la voie adipogénique ne sont pas bien connus. Mieux comprendre comment le tissu adipeux se forme pourrait nous permettre de contrôler son développement et de réduire l'obésité.
Thématique cancer
Les nutriments et les facteurs de croissances sont requis pour le développement des tumeurs. Ces éléments activent l'anabolisme, la croissance et la division cellulaire en activant entre autres la voie mTOR. Les mécanismes fins par lesquels mTOR contrôle l'expression des gènes requis pour le développement des cancers sont encore mal caractérisés. Nous nous intéressons à la découverte de nouveaux facteurs de transcription dont l'action est contrôlée par le sentier signalétique mTOR.
Publications
54- Laplante M, Sabatini DM. mTOR Signaling in Growth Control and Disease.. Cell 2012; 149(2):274-93.
- Bakan I, Laplante M. Connecting mTORC1 signaling to SREBP-1 activation.. Curr Opin Lipidol 2012; 23(3):226-34.
- Li Z, Miard S, Laplante M, Sonenberg N, Picard F. Insulin stimulates IGFBP-2 expression in 3T3-L1 adipocytes through the PI3K/mTOR pathway.. Mol Cell Endocrinol 2012; 358(1):63-8.
- Laplante M, Sabatini DM. mTOR Signaling.. Cold Spring Harb Perspect Biol 2012; 4(2):a011593.
- Laplante M, Horvat S, Festuccia WT, Birsoy K, Prevorsek Z, Efeyan A, Sabatini DM. DEPTOR cell-autonomously promotes adipogenesis, and its expression is associated with obesity.. Cell Metab 2012; 16(2):202-12.
- Birsoy K, Festuccia WT, Laplante M.. A comparative perspective on lipid storage in animals.. J Cell Sci 2013; 126(7):1541-52.
- Laplante M, Sabatini DM.. Regulation of mTORC1 and its impact on gene expression at a glance.. J Cell Sci 2013; 126(8):1713-9.
- Festuccia WT, Pouliot P, Bakan I, Sabatini DM, Laplante M. Myeloid-specific rictor deletion induces m1 macrophage polarization and potentiates in vivo pro-inflammatory response to lipopolysaccharide.. PLoS One 2014; 9(4):e95432.
- Chabot F, Caron A, Laplante M, St-Pierre DH.. Interrelationships between ghrelin, insulin, and glucose homeostasis: physiological relevance.. World J Diabetes 2014; 5(3):328-41.
- Caron A, Baraboi ED, Laplante M, Richard D. DEP domain-containing mTOR-interacting protein in the rat brain: distribution of expression and potential implication.. J Comp Neurol 2015; 523(1):93-107.
- Labbé SM, Caron A, Bakan I, Laplante M, Carpentier AC, Lecomte R, Richard D.. In vivo measurement of energy substrate contribution to cold-induced brown adipose tissue thermogenesis.. FASEB J 2015; 29(5):2046-58.
- Sood A, Jeyaraju DV, Prudent J, Caron A, Lemieux P, McBride HM, Laplante M, Tóth K, Pellegrini L.. A Mitofusin-2-dependent inactivating cleavage of Opa1 links changes in mitochondria cristae and ER contacts in the postprandial liver.. Proc Natl Acad Sci U S A 2015; 111(45):16017-22.
- Caron A, Laplante M. The roles of mTOR complexes in lipid metabolism.. Annu Rev Nutr 2015; 35(0):321-48.
- Sood A, Jeyaraju DV, Prudent J, Caron A, Lemieux P, McBride HM, Laplante M, Tóth K, Pellegrini L. A Mitofusin-2-dependent inactivating cleavage of Opa1 links changes in mitochondria cristae and ER contacts in the postprandial liver.. Proc Natl Acad Sci U S A 2014; 111(45):16017-22.
- Caron A, Labbé SM, Lanfray D, Blanchard PG, Villot R, Roy C, Sabatini DM, Richard D, Laplante M. Mediobasal hypothalamic overexpression of DEPTOR protects against high-fat diet-induced obesity.. Mol Metab 2015; 5(2):102-12.
- Lanfray D, Caron A, Roy MC, Laplante M, Morin F, Leprince J, Tonon MC, Richard D. Involvement of the Acyl-CoA binding domain containing 7 in the control of food intake and energy expenditure in mice.. Elife 2016; 5(0):e11742.
- Labbé SM, Caron A, Chechi K, Laplante M, Lecomte R, Richard D. Metabolic activity of brown, "beige" and white adipose tissues in response to chronic adrenergic stimulation in male mice.. Am J Physiol Endocrinol Metab 2016; 311(1):E260-8.
- Caron A, Labbé SM, Mouchiroud M, Huard R, Richard D, Laplante M. Deptor in POMC neurons affects liver metabolism but is dispensable for the regulation of energy balance.. Am J Physiol Regul Integr Comp Physiol 2016; 310(11):R1322-31.
- Labbé SM, Mouchiroud M, Caron A, Secco B, Freinkman E, Lamoureux G, Gélinas Y, Lecomte R, Bossé Y, Chimin P, Festuccia WT, Richard D, Laplante M. mTORC1 is Required for Brown Adipose Tissue Recruitment and Metabolic Adaptation to Cold.. Sci Rep 2016; 6(0):37223.
- Carbonneau M, M Gagné L, Lalonde ME, Germain MA, Motorina A, Guiot MC, Secco B, Vincent EE, Tumber A, Hulea L, Bergeman J, Oppermann U, Jones RG, Laplante M, Topisirovic I, Petrecca K, Huot MÉ, Mallette FA. The oncometabolite 2-hydroxyglutarate activates the mTOR signalling pathway.. Nat Commun 2016; 7(0):12700.
- Caron A, Labbé SM, Lanfray D, Blanchard PG, Villot R, Roy C, Sabatini DM, Richard D, Laplante M. Mediobasal hypothalamic overexpression of DEPTOR protects against high-fat diet-induced obesity.. Mol Metab 2016; 5(2):102-12.
- Gendron DR, Lecours PB, Lemay AM, Beaulieu MJ, Huppé CA, Lee-Gosselin A, Flamand N, Don AS, Bissonnette É, Blanchet MR, Laplante M, Bourgoin SG, Bossé Y, Marsolais D. A Phosphorylatable Sphingosine Analog Induces Airway Smooth Muscle Cytostasis and Reverses Airway Hyperresponsiveness in Experimental Asthma.. Front Pharmacol 2017; 8(0):78.
- Secco B, Camiré É, Brière MA, Caron A, Billong A, Gélinas Y, Lemay AM, Tharp KM, Lee PL, Gobeil S, Guimond JV, Patey N, Guertin DA, Stahl A, Haddad É, Marsolais D, Bossé Y, Birsoy K, Laplante M. Amplification of Adipogenic Commitment by VSTM2A.. Cell Rep 2017; 18(1):93-106.
- Caron A, Mouchiroud M, Gautier N, Labbé SM, Villot R, Turcotte L, Secco B, Lamoureux G, Shum M, Gélinas Y, Marette A, Richard D, Sabatini DM, Laplante M. Loss of hepatic DEPTOR alters the metabolic transition to fasting.. Mol Metab 2017; 6(5):447-58.
- Wedel J, Bruneau S, Liu K, Kong SW, Sage PT, Sabatini DM, Laplante M, Briscoe DM. DEPTOR modulates activation responses in CD4+ T cells and enhances immunoregulation following transplantation.. Am J Transplant 2019; 19(1):77-88.
- Chechi K, Voisine P, Mathieu P, Laplante M, Bonnet S, Picard F, Joubert P, Richard D. Functional characterization of the Ucp1-associated oxidative phenotype of human epicardial adipose tissue.. Sci Rep 2017; 7(1):15566.
- Wilson AM, Shao Z, Grenier V, Mawambo G, Daudelin JF, Dejda A, Pilon F, Popovic N, Boulet S, Parinot C, Oubaha M, Labrecque N, de Guire V, Laplante M, Lettre G, Sennlaub F, Joyal JS, Meunier M, Sapieha P. Neuropilin-1 expression in adipose tissue macrophages protects against obesity and metabolic syndrome.. Sci Immunol 2018; 3(21):4626.
- Caron A, Briscoe DM, Richard D, Laplante M. DEPTOR at the Nexus of Cancer, Metabolism, and Immunity.. Physiol Rev 2018; 98(3):1765-1803.
- Carter S, Miard S, Caron A, Sallé-Lefort S, St-Pierre P, Anhê FF, Lavoie-Charland E, Blais-Lecours P, Drolet MC, Lefebvre JS, Lacombe J, Deshaies Y, Couet J, Laplante M, Ferron M, Bossé Y, Marette A, Richard D, Marsolais D, Picard F. Loss of OcaB Prevents Age-Induced Fat Accretion and Insulin Resistance by Altering B-Lymphocyte Transition and Promoting Energy Expenditure.. Diabetes 2018; 67(7):1285-1296.
- Issa N, Lachance G, Bellmann K, Laplante M, Stadler K, Marette A. Cytokines promote lipolysis in 3T3-L1 adipocytes through induction of NADPH oxidase 3 expression and superoxide production.. J Lipid Res 2018; 59(12):2321-2328.
- Clemenceau A, Boucherat O, Landry-Truchon K, Lamontagne M, Biardel S, Joubert P, Gobeil S, Secco B, Laplante M, Morissette M, Obeidat M, Timens W, Jeannotte L, Bossé Y.. Lung cancer susceptibility genetic variants modulate HOXB2 expression in the lung.. Int J Dev Biol 2018; 62(11):857-864.
- Girard R, Darsigny M, Jones C, Maloum-Rami F, Gélinas Y, Carpentier AC, Laplante M, Perreault N, Boudreau F. HNF4? is a novel regulator of intestinal glucose-dependent insulinotropic polypeptide.. Sci Rep 2019; 9(1):4200.
- Besse-Patin A, Jeromson S, Levesque-Damphousse P, Secco B, Laplante M, Estall JL. PGC1A regulates the IRS1:IRS2 ratio during fasting to influence hepatic metabolism downstream of insulin.. Proc Natl Acad Sci U S A 2019; 116(10):4285-4290.
- Jubinville É, Routhier J, Maranda-Robitaille M, Pineault M, Milad N, Talbot M, Beaulieu MJ, Aubin S, Paré MÈ, Laplante M, Morissette MC. Pharmacological activation of Liver X Receptor during cigarette smoke exposure adversely affects alveolar macrophages and pulmonary surfactant homeostasis.. Am J Physiol Lung Cell Mol Physiol 2019; 316(4):L669-L678.
- Mouchiroud M, Camiré É, Aldow M, Caron A, Jubinville É, Turcotte L, Kaci I, Beaulieu MJ, Roy C, Labbé SM, Varin TV, Gélinas Y, Lamothe J, Trottier J, Mitchell PL, Guénard F, Festuccia WT, Joubert P, Rose CF, Karvellas CJ, Barbier O, Morissette MC, Marette A, Laplante M. The hepatokine Tsukushi is released in response to NAFLD and impacts cholesterol homeostasis.. JCI Insight 2019; 4(15):129492.
- Mouchiroud M, Camiré É, Aldow M, Caron A, Jubinville É, Turcotte L, Kaci I, Beaulieu MJ, Roy C, Labbé SM, Varin TV, Gélinas Y, Lamothe J, Trottier J, Mitchell PL, Guénard F, Festuccia WT, Joubert P, Rose CF, Karvellas CJ, Barbier O, Morissette MC, Marette A, Laplante M. The Hepatokine TSK does not affect brown fat thermogenic capacity, body weight gain, and glucose homeostasis.. Mol Metab 2019; 30(0):184-191.
- Marcouiller F, Jochmans-Lemoine A, Ganouna-Cohen G, Mouchiroud M, Laplante M, Marette A, Bairam A, Joseph V. Metabolic Responses to Intermittent Hypoxia Are Regulated By Sex And Estradiol In Mice.. Am J Physiol Endocrinol Metab 2021; 320(2):E316-E325.
- Al Dow M, Silveira MAD, Poliquin A, Tribouillard L, Fournier É, Trébaol E, Secco B, Villot R, Tremblay F, Bilodeau S, Laplante M. Control of adipogenic commitment by a STAT3-VSTM2A axis.. Am J Physiol Endocrinol Metab 2021; 320(2):E259-E269.
- Jubinville É, Milad N, Maranda-Robitaille M, Lafrance MA, Pineault M, Lamothe J, Routhier J, Beaulieu MJ, Aubin S, Laplante M, Morissette MC. Critical importance of dietary methionine and choline in the maintenance of lung homeostasis during normal and cigarette smoke exposure conditions.. Am J Physiol Lung Cell Mol Physiol 2020; 319(2):L391-L402.
- Agudelo D, Carter S, Velimirovic M, Duringer A, Rivest JF, Levesque S, Loehr J, Mouchiroud M, Cyr D, Waters PJ, Laplante M, Moineau S, Goulet A, Doyon Y. Versatile and robust genome editing with Streptococcus thermophilus CRISPR1-Cas9.. Genome Res 2020; 30(1):107-117.
- Villot R, Poirier A, Bakan I, Boulay K, Fernández E, Devillers R, Gama-Braga L, Tribouillard L, Gagné A, Duchesne É, Caron D, Bérubé JS, Bérubé JC, Coulombe Y, Orain M, Gélinas Y, Gobeil S, Bossé Y, Masson JY, Elowe S, Bilodeau S, Manem V, Joubert P, Mallette FA, Laplante M. ZNF768 links oncogenic RAS to cellular senescence.. Nat Commun 2021; 12(1):4841.
- Poirier A, Gagné A, Laflamme P, Marcoux M, Orain M, Plante S, Joubert D, Joubert P, Laplante M. ZNF768 Expression Associates with High Proliferative Clinicopathological Features in Lung Adenocarcinoma.. Cancers (Basel) 2021; 13(16):4136.
- de la Calle Arregui C, Plata-Gómez AB, Deleyto-Seldas N, García F, Ortega-Molina A, Abril-Garrido J, Rodriguez E, Nemazanyy I, Tribouillard L, de Martino A, Caleiras E, Campos-Olivas R, Mulero F, Laplante M, Muñoz J, Pende M, Sabio G, Sabatini DM, Efeyan A. Limited survival and impaired hepatic fasting metabolism in mice with constitutive Rag GTPase signaling.. Nat Commun 2021; 12(1):3660.
- Castro É, Vieira TS, Oliveira TE, Ortiz-Silva M, Andrade ML, Tomazelli CA, Peixoto AS, Sobrinho CR, Moreno MF, Gilio GR, Moreira RJ, Guimarães RC, Perandini LA, Chimin P, Reckziegel P, Moretti EH, Steiner AA, Laplante M, Festuccia WT. Adipocyte-specific mTORC2 deficiency impairs BAT and iWAT thermogenic capacity without affecting glucose uptake and energy expenditure in cold-acclimated mice.. Am J Physiol Endocrinol Metab 2021; 321(5):E592-E605.
- Vilela VR, Samson N, Nachbar R, Perazza LR, Lachance G, Rokatoarivelo V, Centano-Baez C, Zancan P, Sola-Penna M, Bellmann K, Di Marzo V, Laplante M, Marette A. Adipocyte-specific Nos2 deletion improves insulin resistance and dyslipidemia through brown fat activation in diet-induced obese mice.. Mol Metab 2022; 0(0):101437.
- Lechasseur A, Mouchiroud M, Tremblay F, Bouffard G, Milad N, Pineault M, Maranda-Robitaille M, Routhier J, Beaulieu MJ, Aubin S, Laplante M, Morissette MC. Glycerol contained in vaping liquids affects the liver and aspects of energy homeostasis in a sex-dependent manner.. Physiol Rep 2022; 10(2):e15146.
- Girard R, Tremblay S, Noll C, St-Jean S, Jones C, Gélinas Y, Maloum-Rami F, Perreault N, Laplante M, Carpentier AC, Boudreau F. The transcription factor hepatocyte nuclear factor 4A acts in the intestine to promote white adipose tissue energy storage.. Nat Commun 2022; 13(1):224.
- Shin HR, Citron YR, Wang L, Tribouillard L, Goul CS, Stipp R, Sugasawa Y, Jain A, Samson N, Lim CY, Davis OB, Castaneda-Carpio D, Qian M, Nomura DK, Perera RM, Park E, Covey DF, Laplante M, Evers AS, Zoncu R. Lysosomal GPCR-like protein LYCHOS signals cholesterol sufficiency to mTORC1.. Science 2022; 377(6612):1290-1298.
- Tribouillard L, Laplante M. mTORC1 takes control of lysosomal lipid breakdown.. Nat Metab 2022; 4(12):1620-1622.
- Daoust L, Choi BS, Agrinier AL, Varin TV, Ouellette A, Mitchell PL, Samson N, Pilon G, Levy E, Desjardins Y, Laplante M, Forato Anhê F, Houde VP, Marette A. Gnotobiotic mice housing conditions critically influence the phenotype associated with transfer of faecal microbiota in a context of obesity.. Gut 2023; 72(5):896-905.
- Kumar A, Schwab M, Laborit Labrada B, Silveira MAD, Goudreault M, Fournier É, Bellmann K, Beauchemin N, Gingras AC, Bilodeau S, Laplante M, Marette A. SHP-1 phosphatase acts as a coactivator of PCK1 transcription to control gluconeogenesis.. J Biol Chem 2023; 299(9):105164.
- Villot R, Poirier A, Devillers R, Kolnoguz , Elowe S, Manem VSK, Joubert P, Mallette FA, Laplante M.. ZNF768: controlling cellular senescence and proliferation with ten fingers. Mol Cell Oncol 2021; 8(6):1985930.
- Colas C, Mouchiroud M, Al Dow M, Kolnohuz A, Gélinas Y, Caron A, Laplante M. DEPTOR loss impairs brown adipocyte development in vitro but has limited impacts in mice.. Mol Metab 2023; 67(0):101660.
- Gunes A, Schmitt C, Bilodeau L, Huet C, Belblidia A, Baldwin C, Giard JM, Biertho L, Lafortune-Payette A, Couture CY, Cheung A, Nguyen BN, Galun E, Bémeur C, Bilodeau M, Laplante M, Tang A, Faraj M, Estall JL. IL-6 Trans-Signaling Is Increased in Diabetes, Impacted by Glucolipotoxicity, and Associated With Liver Stiffness and Fibrosis in Fatty Liver Disease.. Diabetes 2023; 72(12):1820-1834.
