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2. Maresin 1 activates brown adipose tissue and promotes browning of white adipose tissue in mice

Author

Laiglesia, Laura M., Escoté, Xavier, Sáinz, Neira, Felix-Soriano, Elisa, Santamaría, Eva, Collantes, María, Fernández-Galilea, Marta, Colón-Mesa, Ignacio, Martínez-Fernández, Leyre, Quesada-López, Tania, Quesada-Vázquez, Sergio, Rodríguez-Ortigosa, Carlos, Arbones-Mainar, José M., Valverde, Ángela M., Martínez, J Alfredo, Dalli, Jesmond, Herrero, Laura, Lorente-Cebrián, Silvia, Villarroya, Francesc, and Moreno-Aliaga, María J.

Published
2023
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6. Maresin 1 activates brown adipose tissue and promotes browning of white adipose tissue in mice

Author

Ministerio de Ciencia e Innovación (España), Agencia Estatal de Investigación (España), Ministerio de Economía y Competitividad (España), Ministerio de Ciencia, Innovación y Universidades (España), Diputación Foral de Navarra, Fundación Merck Salud, Instituto de Salud Carlos III, Asociación de Amigos de la Universidad de Navarra, Universidad de Navarra, Fundación la Caixa, Laiglesia, Laura M., Escoté, Xavier, Sáinz, Neira, Felix-Soriano, Elisa, Santamaría, Eva, Collantes, María, Fernández-Galilea, Marta, Colón-Mesa, Ignacio, Martínez-Fernández, Leyre, Quesada-López, Tania, Quesada-Vázquez, Sergio, Rodríguez-Ortigosa, Carlos, Arbones-Mainar, José M., Valverde, Ángela M., Martínez, J. Alfredo, Dalli, Jesmond, Herrero, Laura, Lorente-Cebrián, Silvia, Villarroya, Francesc, Moreno-Aliaga, María Jesús, Ministerio de Ciencia e Innovación (España), Agencia Estatal de Investigación (España), Ministerio de Economía y Competitividad (España), Ministerio de Ciencia, Innovación y Universidades (España), Diputación Foral de Navarra, Fundación Merck Salud, Instituto de Salud Carlos III, Asociación de Amigos de la Universidad de Navarra, Universidad de Navarra, Fundación la Caixa, Laiglesia, Laura M., Escoté, Xavier, Sáinz, Neira, Felix-Soriano, Elisa, Santamaría, Eva, Collantes, María, Fernández-Galilea, Marta, Colón-Mesa, Ignacio, Martínez-Fernández, Leyre, Quesada-López, Tania, Quesada-Vázquez, Sergio, Rodríguez-Ortigosa, Carlos, Arbones-Mainar, José M., Valverde, Ángela M., Martínez, J. Alfredo, Dalli, Jesmond, Herrero, Laura, Lorente-Cebrián, Silvia, Villarroya, Francesc, and Moreno-Aliaga, María Jesús

Abstract

[Objective]: 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.

Published
2023

8. List of Contributors

Author

Abete, Itziar, primary, Aguilera, Concepción M., additional, Alfredo Martínez, J., additional, Alonso-Pedrero, Lucia, additional, Angeles Zulet, M., additional, Anguita-Ruiz, Augusto, additional, Arredondo-Olguín, Miguel, additional, Bullón-Vela, M. Vanessa, additional, Casuso, Rafael A., additional, Catalán, Victoria, additional, Escasany, Elia, additional, Escoté, Xavier, additional, Felix-Soriano, Elisa, additional, Fernández-Galilea, Marta, additional, Frühbeck, Gema, additional, Gil, Ángel, additional, Gómez-Ambrosi, Javier, additional, Gomez-Llorente, Carolina, additional, González-Muniesa, Pedro, additional, Huertas, Jesús R., additional, Izquierdo-Lahuerta, Adriana, additional, López-López, Paulina, additional, Marti del Moral, Amelia, additional, Martínez-Fernández, Leyre, additional, Medina-Gómez, Gema, additional, Mesa-Garcia, Maria D., additional, Morell-Azanza, Lydia, additional, Moreno-Aliaga, María J., additional, Ojeda-Rodriguez, Ana, additional, Olza, Josune, additional, Pastor-Villaescusa, Belén, additional, Pejenaute, Álvaro, additional, Plaza-Diaz, Julio, additional, Pons, Antoni, additional, Rangel-Huerta, Oscar D., additional, Rojas-Sobarzo, Loreto, additional, Ruiz-Ojeda, Francisco J., additional, Rupérez, Azahara I., additional, Sanchez Rodriguez, Estefania, additional, Sureda, Antoni, additional, Tur, Josep A., additional, and Zalba Goñi, Guillermo, additional

Published
2018
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14. Lipoprotein receptor SR-B1 deficiency enhances adipose tissue inflammation and reduces susceptibility to hepatic steatosis during diet-induced obesity in mice

Author

Rivera, Katherine, primary, Quiñones, Verónica, additional, Amigo, Ludwig, additional, Santander, Nicolás, additional, Salas-Pérez, Francisca, additional, Xavier, Aline, additional, Fernández-Galilea, Marta, additional, Carrasco, Gonzalo, additional, Cabrera, Daniel, additional, Arrese, Marco, additional, Busso, Dolores, additional, Andia, Marcelo E., additional, and Rigotti, Attilio, additional

Published
2021
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25. α-Lipoic acid reduces fatty acid esterification and lipogenesis in adipocytes from overweight/obese subjects

Author

Fernández-Galilea, Marta, Pérez-Matute, Patricia, Prieto-Hontoria, Pedro L., Sáinz, Neira, López-Yoldi, Miguel, Houssier, Marianne, Martínez, J. Alfredo, Langin, Dominique, and Moreno-Aliaga, María J.

Subjects
Esterification, Thioctic Acid, Lipogenesis, Fatty Acids, Subcutaneous Fat, Down-Regulation, Overweight, Lipid Metabolism, Adipocytes, Humans, Female, Obesity, Cells, Cultured, Triglycerides
Abstract

Objective: -Lipoic acid (-LA) is a natural occurring antioxidant with beneficial effects on obesity. The aim of this study was to investigate the putative effects of -LA on triglyceride accumulation and lipogenesis in subcutaneous adipocytes from overweight/obese subjects and to determine the potential mechanisms involved. Methods: Fully differentiated human subcutaneous adipocytes were treated with -LA (100 and 250 M) during 24 h for studying triglyceride content, de novo lipogenesis, and levels of key lipogenic enzymes. The involvement of AMP-activated protein kinase (AMPK) activation was also evaluated. Results: -LA down-regulated triglyceride content by inhibiting fatty acid esterification and de novo lipogenesis. These effects were mediated by reduction in fatty acid synthase (FAS), stearoyl-coenzyme A desaturase 1, and diacylglycerol O-acyltransferase 1 protein levels. Interestingly, -LA increased AMPK and acetyl CoA carboxylase phosphorylation, while the presence of the AMPK inhibitor Compound C reversed the inhibition observed on FAS protein levels. Conclusions: -LA down-regulates key lipogenic enzymes, inhibiting lipogenesis and reducing triglyceride accumulation through the activation of AMPK signaling pathway in human subcutaneous adipocytes from overweight/obese subjects.

Published
2014

29. Biology and pathological implications of brown adipose tissue: promises and caveats for the control of obesity and its associated complications.

Author

Tapia, Pablo, Fernández‐Galilea, Marta, Robledo, Fermín, Cortés, Víctor A., Galgani, José E., and Mardones, Pablo

Subjects
*BROWN adipose tissue, *ADIPOGENESIS, *BODY temperature regulation, *OBESITY, *INSULIN resistance
Abstract

ABSTRACT: The discovery of metabolically active brown adipose tissue (BAT) in adult humans has fuelled the research of diverse aspects of this previously neglected tissue. BAT is solely present in mammals and its clearest physiological role is non‐shivering thermogenesis, owing to the capacity of brown adipocytes to dissipate metabolic energy as heat. Recently, a number of other possible functions have been proposed, including direct regulation of glucose and lipid homeostasis and the secretion of a number of factors with diverse regulatory actions. Herein, we review recent advances in general biological knowledge of BAT and discuss the possible implications of this tissue in human metabolic health. In particular, we confront the claimed thermogenic potential of BAT for human energy balance and body mass regulation, mostly based on animal studies, with the most recent quantifications of human BAT. [ABSTRACT FROM AUTHOR]

Published
2018
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