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

15 Citations (Scopus)

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

Funding

This work has been supported by grants from FEDER/Ministerio de Ciencia, Innovación y Universidades-Agencia Estatal de Investigación ( CD: BFU2017-87721 ; RN: RTI2018-099413-B-I00 ; Xunta de Galicia (RN: 2015-CP080 and 2016-PG057 ) and ED431G 2019/02 , Fundación BBVA (RN), Fundación Atresmedia (RN), European Foundation for the Study of Diabetes (RN), “la Caixa” Foundation ( ID 100010434 ; under the agreements LCF/PR/HR19/52160016 to RN/MC and LCF/PR/HR19/52160022 to ML), Helse Vest RHF (JF: Western Norway Regional Health Authority) and Xunta de Galicia ( MQ: 2018-PG013 ). The research leading to these results has also received funding from the European Community's H2020 Framework Programme under the following grants: ERC Synergy Grant-2019-WATCH- 810331 to RN, VP and MS and ERC Consolidator Grant MITOSENSING-725004 to MC. CIBERobn is an initiative of the Instituto de Salud Carlos III (ISCIII) of Spain which is supported by FEDER funds. M.Q. is a recipient of a Postdoctoral contract from Galician Government (Xunta de Galicia ED481B2018/004 ). OA-M was funded by a research contract Miguel Servet ( CP20/00146 ) from the ISCIII .

UN SDGs

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

SDG 3 Good Health and Well-being

Research Areas and Centers

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

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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",

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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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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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