Sirt3 in POMC neurons controls energy balance in a sex- and diet-dependent manner

Mar Quiñones; René Hernández-Bautista; Daniel Beiroa; Violeta Heras; Francisco L. Torres-Leal; Brian Y.H. Lam; Ana Senra; Johan Fernø; Alicia García Gómez-Valadés; Markus Schwaninger; Vincent Prevot; Giles Yeo; Marc Claret; Miguel López; Carlos Diéguez; Omar Al-Massadi; Ruben Nogueiras

doi:10.1016/j.redox.2021.101945

Sirt3 in POMC neurons controls energy balance in a sex- and diet-dependent manner

Mar Quiñones, René Hernández-Bautista, Daniel Beiroa, Violeta Heras, Francisco L. Torres-Leal, Brian Y.H. Lam, Ana Senra, Johan Fernø, Alicia García Gómez-Valadés, Markus Schwaninger, Vincent Prevot, Giles Yeo, Marc Claret, Miguel López, Carlos Diéguez, Omar Al-Massadi, Ruben Nogueiras^*

^*Corresponding author for this work

Institute of Experimental and Clinical Pharmacology and Toxicology

Abstract

Sirtuin 3 (SIRT3) is one of the seven mammalian sirtuin homologs of the yeast Sir2 gene that has emerged as an important player in the regulation of energy metabolism in peripheral tissues. However, its role in the hypothalamus has not been explored. Herein, we show that the genetic inhibition of SIRT3 in the hypothalamic arcuate nucleus (ARC) induced a negative energy balance and improvement of several metabolic parameters. These effects are specific for POMC neurons, because ablation of SIRT3 in POMC, but not in AgRP neurons, decreased body weight and adiposity, increased energy expenditure and brown adipose tissue (BAT) activity, and induced browning in white adipose tissue (WAT). Notably, the depletion of SIRT3 in POMC neurons caused these effects in male mice fed a chow diet but failed to affect energy balance in males fed a high fat diet and females under both type of diets. Overall, we provide the first evidence pointing for a key role of SIRT3 in POMC neurons in the regulation of energy balance.

Original language	English
Article number	101945
Journal	Redox Biology
Volume	41
Pages (from-to)	101945
ISSN	2213-2317
DOIs	https://doi.org/10.1016/j.redox.2021.101945
Publication status	Published - 05.2021

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Academic Focus: Center for Brain, Behavior and Metabolism (CBBM)

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This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1016/j.redox.2021.101945

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Quiñones, M., Hernández-Bautista, R., Beiroa, D., Heras, V., Torres-Leal, F. L., Lam, B. Y. H., Senra, A., Fernø, J., Gómez-Valadés, A. G., Schwaninger, M., Prevot, V., Yeo, G., Claret, M., López, M., Diéguez, C., Al-Massadi, O., & Nogueiras, R. (2021). Sirt3 in POMC neurons controls energy balance in a sex- and diet-dependent manner. Redox Biology, 41, 101945. Article 101945. https://doi.org/10.1016/j.redox.2021.101945

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title = "Sirt3 in POMC neurons controls energy balance in a sex- and diet-dependent manner",

abstract = "Sirtuin 3 (SIRT3) is one of the seven mammalian sirtuin homologs of the yeast Sir2 gene that has emerged as an important player in the regulation of energy metabolism in peripheral tissues. However, its role in the hypothalamus has not been explored. Herein, we show that the genetic inhibition of SIRT3 in the hypothalamic arcuate nucleus (ARC) induced a negative energy balance and improvement of several metabolic parameters. These effects are specific for POMC neurons, because ablation of SIRT3 in POMC, but not in AgRP neurons, decreased body weight and adiposity, increased energy expenditure and brown adipose tissue (BAT) activity, and induced browning in white adipose tissue (WAT). Notably, the depletion of SIRT3 in POMC neurons caused these effects in male mice fed a chow diet but failed to affect energy balance in males fed a high fat diet and females under both type of diets. Overall, we provide the first evidence pointing for a key role of SIRT3 in POMC neurons in the regulation of energy balance.",

author = "Mar Qui{\~n}ones and Ren{\'e} Hern{\'a}ndez-Bautista and Daniel Beiroa and Violeta Heras and Torres-Leal, {Francisco L.} and Lam, {Brian Y.H.} and Ana Senra and Johan Fern{\o} and G{\'o}mez-Valad{\'e}s, {Alicia Garc{\'i}a} and Markus Schwaninger and Vincent Prevot and Giles Yeo and Marc Claret and Miguel L{\'o}pez and Carlos Di{\'e}guez and Omar Al-Massadi and Ruben Nogueiras",

note = "Publisher Copyright: {\textcopyright} 2021 The Author(s)",

year = "2021",

month = may,

doi = "10.1016/j.redox.2021.101945",

language = "English",

volume = "41",

pages = "101945",

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Quiñones, M, Hernández-Bautista, R, Beiroa, D, Heras, V, Torres-Leal, FL, Lam, BYH, Senra, A, Fernø, J, Gómez-Valadés, AG, Schwaninger, M, Prevot, V, Yeo, G, Claret, M, López, M, Diéguez, C, Al-Massadi, O & Nogueiras, R 2021, 'Sirt3 in POMC neurons controls energy balance in a sex- and diet-dependent manner', Redox Biology, vol. 41, 101945, pp. 101945. https://doi.org/10.1016/j.redox.2021.101945

TY - JOUR

T1 - Sirt3 in POMC neurons controls energy balance in a sex- and diet-dependent manner

AU - Quiñones, Mar

AU - Hernández-Bautista, René

AU - Beiroa, Daniel

AU - Heras, Violeta

AU - Torres-Leal, Francisco L.

AU - Lam, Brian Y.H.

AU - Senra, Ana

AU - Fernø, Johan

AU - Gómez-Valadés, Alicia García

AU - Schwaninger, Markus

AU - Prevot, Vincent

AU - Yeo, Giles

AU - Claret, Marc

AU - López, Miguel

AU - Diéguez, Carlos

AU - Al-Massadi, Omar

AU - Nogueiras, Ruben

PY - 2021/5

Y1 - 2021/5

N2 - Sirtuin 3 (SIRT3) is one of the seven mammalian sirtuin homologs of the yeast Sir2 gene that has emerged as an important player in the regulation of energy metabolism in peripheral tissues. However, its role in the hypothalamus has not been explored. Herein, we show that the genetic inhibition of SIRT3 in the hypothalamic arcuate nucleus (ARC) induced a negative energy balance and improvement of several metabolic parameters. These effects are specific for POMC neurons, because ablation of SIRT3 in POMC, but not in AgRP neurons, decreased body weight and adiposity, increased energy expenditure and brown adipose tissue (BAT) activity, and induced browning in white adipose tissue (WAT). Notably, the depletion of SIRT3 in POMC neurons caused these effects in male mice fed a chow diet but failed to affect energy balance in males fed a high fat diet and females under both type of diets. Overall, we provide the first evidence pointing for a key role of SIRT3 in POMC neurons in the regulation of energy balance.

AB - Sirtuin 3 (SIRT3) is one of the seven mammalian sirtuin homologs of the yeast Sir2 gene that has emerged as an important player in the regulation of energy metabolism in peripheral tissues. However, its role in the hypothalamus has not been explored. Herein, we show that the genetic inhibition of SIRT3 in the hypothalamic arcuate nucleus (ARC) induced a negative energy balance and improvement of several metabolic parameters. These effects are specific for POMC neurons, because ablation of SIRT3 in POMC, but not in AgRP neurons, decreased body weight and adiposity, increased energy expenditure and brown adipose tissue (BAT) activity, and induced browning in white adipose tissue (WAT). Notably, the depletion of SIRT3 in POMC neurons caused these effects in male mice fed a chow diet but failed to affect energy balance in males fed a high fat diet and females under both type of diets. Overall, we provide the first evidence pointing for a key role of SIRT3 in POMC neurons in the regulation of energy balance.

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U2 - 10.1016/j.redox.2021.101945

DO - 10.1016/j.redox.2021.101945

M3 - Journal articles

C2 - 33744652

AN - SCOPUS:85102627327

SN - 2213-2317

VL - 41

SP - 101945

JO - Redox Biology

JF - Redox Biology

M1 - 101945

ER -

Sirt3 in POMC neurons controls energy balance in a sex- and diet-dependent manner

Abstract

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