000127695 001__ 127695
000127695 005__ 20240705134221.0
000127695 0247_ $$2doi$$a10.1016/j.molmet.2023.101749
000127695 0248_ $$2sideral$$a134652
000127695 037__ $$aART-2023-134652
000127695 041__ $$aeng
000127695 100__ $$aLaiglesia, Laura M.
000127695 245__ $$aMaresin 1 activates brown adipose tissue and promotes browning of white adipose tissue in mice
000127695 260__ $$c2023
000127695 5060_ $$aAccess copy available to the general public$$fUnrestricted
000127695 5203_ $$aObjective: Maresin 1 (MaR1) is a docosahexaenoic acid-derived proresolving lipid mediator with insulin-sensitizing and anti-steatosis properties. Here, we aim to unravel MaR1 actions on brown adipose tissue (BAT) activation and white adipose tissue (WAT) browning.
Methods: MaR1 actions were tested in cultured murine brown adipocytes and in human mesenchymal stem cells (hMSC)-derived adipocytes. In vivo effects of MaR1 were tested in diet-induced obese (DIO) mice and lean WT and Il6 knockout (Il6−/−) mice.
Results: In cultured differentiated murine brown adipocytes, MaR1 reduces the expression of inflammatory genes, while stimulates glucose uptake, fatty acid utilization and oxygen consumption rate, along with the upregulation of mitochondrial mass and genes involved in mitochondrial biogenesis and function and the thermogenic program. In Leucine Rich Repeat Containing G Protein-Coupled Receptor 6 (LGR6)-depleted brown adipocytes using siRNA, the stimulatory effect of MaR1 on thermogenic genes was abrogated. In DIO mice, MaR1 promotes BAT remodeling, characterized by higher expression of genes encoding for master regulators of mitochondrial biogenesis and function and iBAT thermogenic activation, together with increased M2 macrophage markers. In addition, MaR1-treated DIO mice exhibit a better response to cold-induced BAT activation. Moreover, MaR1 induces a beige adipocyte signature in inguinal WAT of DIO mice and in hMSC-derived adipocytes. MaR1 potentiates Il6 expression in brown adipocytes and BAT of cold exposed lean WT mice. Interestingly, the thermogenic properties of MaR1 were abrogated in Il6−/− mice.
Conclusions: These data reveal MaR1 as a novel agent that promotes BAT activation and WAT browning by regulating thermogenic program in adipocytes and M2 polarization of macrophages. Moreover, our data suggest that LGR6 receptor is mediating MaR1 actions on brown adipocytes, and that IL-6 is required for the thermogenic effects of MaR1.
000127695 536__ $$9info:eu-repo/grantAgreement/ES/MICINN /BFU2012-36089$$9info:eu-repo/grantAgreement/ES/MICINN /BFU2015-65937-R$$9info:eu-repo/grantAgreement/ES/MICINN/PID2019-106982RB-I00
000127695 540__ $$9info:eu-repo/semantics/openAccess$$aby-nc-nd$$uhttp://creativecommons.org/licenses/by-nc-nd/3.0/es/
000127695 592__ $$a3.034$$b2023
000127695 593__ $$aMolecular Biology$$c2023$$dQ1
000127695 593__ $$aCell Biology$$c2023$$dQ1
000127695 655_4 $$ainfo:eu-repo/semantics/article$$vinfo:eu-repo/semantics/publishedVersion
000127695 700__ $$aEscoté, Xavier
000127695 700__ $$aSáinz, Neira
000127695 700__ $$aFelix-Soriano, Elisa
000127695 700__ $$aSantamaría, Eva
000127695 700__ $$aCollantes, María
000127695 700__ $$aFernández-Galilea, Marta
000127695 700__ $$aColón-Mesa, Ignacio
000127695 700__ $$aMartínez-Fernández, Leyre
000127695 700__ $$aQuesada-López, Tania
000127695 700__ $$aQuesada-Vázquez, Sergio
000127695 700__ $$aRodríguez-Ortigosa, Carlos
000127695 700__ $$0(orcid)0000-0002-8982-3737$$aArbones-Mainar, José M.
000127695 700__ $$aValverde, Ángela M.
000127695 700__ $$aMartínez, J Alfredo
000127695 700__ $$aDalli, Jesmond
000127695 700__ $$aHerrero, Laura
000127695 700__ $$0(orcid)0000-0002-1033-6152$$aLorente-Cebrián, Silvia$$uUniversidad de Zaragoza
000127695 700__ $$aVillarroya, Francesc
000127695 700__ $$aMoreno-Aliaga, María J.
000127695 7102_ $$11012$$2410$$aUniversidad de Zaragoza$$bDpto. Farmac.Fisiol.y Med.L.F.$$cÁrea Fisiología
000127695 773__ $$g74 (2023), 101749 [14 pp.]$$pMolecular metabolism.$$tMolecular Metabolism$$x2212-8778
000127695 8564_ $$s2408723$$uhttps://zaguan.unizar.es/record/127695/files/texto_completo.pdf$$yVersión publicada
000127695 8564_ $$s2723828$$uhttps://zaguan.unizar.es/record/127695/files/texto_completo.jpg?subformat=icon$$xicon$$yVersión publicada
000127695 909CO $$ooai:zaguan.unizar.es:127695$$particulos$$pdriver
000127695 951__ $$a2024-07-05-12:54:18
000127695 980__ $$aARTICLE