Brown adipose tissue (BAT) activity plays a key role in regulating systemic energy. The activation of BAT results in increased energy expenditure, making this tissue an attractive pharmacological target for therapies against obesity and type 2 diabetes. Sirtuin 5 (SIRT5) affects BAT function by regulating adipogenic transcription factor expression and mitochondrial respiration. We analyzed the expression of SIRT5 in the different adipose depots of mice. We treated 3T3-L1 preadipocytes and mouse primary preadipocyte cultures with the SIRT5 inhibitor MC3482 and investigated the effects of this compound on adipose differentiation and function. The administration of MC3482 during the early stages of differentiation promoted the expression of brown adipocyte and mitochondrial biogen-esis markers. Upon treatment with MC3482, 3T3-L1 adipocytes showed an increased activation of the AMP-activated protein kinase (AMPK), which is known to stimulate brown adipocyte differentiation. This effect was paralleled by an increase in autophagic/mitophagic flux and a reduction in lipid droplet size, mediated by a higher lipolytic rate. Of note, MC3482 increased the expression and the activity of adipose triglyceride lipase, without modulating hormone-sensitive lipase. Our findings reveal that SIRT5 inhibition stimulates brown adipogenesis in vitro, supporting this approach as a strategy to stimulate BAT and counteract obesity.

Sirt5 inhibition induces brown fat-like phenotype in 3t3-l1 preadipocytes / Molinari, Francesca; Feraco, Alessandra; Mirabilii, Simone; Saladini, Serena; Sansone, Luigi; Vernucci, Enza; Tomaselli, Giada; Marzolla, Vincenzo; Rotili, Dante; A Russo, Matteo; Ricciardi, Maria Rosaria; Tafuri, Agostino; Mai, Antonello; Caprio, Massimiliano; Tafani, Marco; Armani, Andrea. - In: CELLS. - ISSN 2073-4409. - 10:5(2021), pp. 1-17. [10.3390/cells10051126]

Sirt5 inhibition induces brown fat-like phenotype in 3t3-l1 preadipocytes

Simone Mirabilii;Dante Rotili;Maria Rosaria Ricciardi;Agostino Tafuri;Antonello Mai;Marco Tafani;
2021

Abstract

Brown adipose tissue (BAT) activity plays a key role in regulating systemic energy. The activation of BAT results in increased energy expenditure, making this tissue an attractive pharmacological target for therapies against obesity and type 2 diabetes. Sirtuin 5 (SIRT5) affects BAT function by regulating adipogenic transcription factor expression and mitochondrial respiration. We analyzed the expression of SIRT5 in the different adipose depots of mice. We treated 3T3-L1 preadipocytes and mouse primary preadipocyte cultures with the SIRT5 inhibitor MC3482 and investigated the effects of this compound on adipose differentiation and function. The administration of MC3482 during the early stages of differentiation promoted the expression of brown adipocyte and mitochondrial biogen-esis markers. Upon treatment with MC3482, 3T3-L1 adipocytes showed an increased activation of the AMP-activated protein kinase (AMPK), which is known to stimulate brown adipocyte differentiation. This effect was paralleled by an increase in autophagic/mitophagic flux and a reduction in lipid droplet size, mediated by a higher lipolytic rate. Of note, MC3482 increased the expression and the activity of adipose triglyceride lipase, without modulating hormone-sensitive lipase. Our findings reveal that SIRT5 inhibition stimulates brown adipogenesis in vitro, supporting this approach as a strategy to stimulate BAT and counteract obesity.
adipogenesis; adipose tissue; mitochondrial function; obesity; sirtuins
01 Pubblicazione su rivista::01a Articolo in rivista
Sirt5 inhibition induces brown fat-like phenotype in 3t3-l1 preadipocytes / Molinari, Francesca; Feraco, Alessandra; Mirabilii, Simone; Saladini, Serena; Sansone, Luigi; Vernucci, Enza; Tomaselli, Giada; Marzolla, Vincenzo; Rotili, Dante; A Russo, Matteo; Ricciardi, Maria Rosaria; Tafuri, Agostino; Mai, Antonello; Caprio, Massimiliano; Tafani, Marco; Armani, Andrea. - In: CELLS. - ISSN 2073-4409. - 10:5(2021), pp. 1-17. [10.3390/cells10051126]
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11573/1576703
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