Sex-specific genetic regulation of adipose mitochondria and metabolic syndrome by Ndufv2.

Adipose Tissue / metabolism Adiposity / genetics Animals Biomarkers Cell Respiration / genetics Chromosomes, Human, Pair 17 Disease Models, Animal Disease Susceptibility Female Gene Expression Profiling Gene Expression Regulation Genetic Association Studies Humans Male Metabolic Syndrome / diagnosis Mice Mitochondria / genetics NADH Dehydrogenase / genetics Polymorphism, Single Nucleotide Quantitative Trait Loci Quantitative Trait, Heritable Reactive Oxygen Species / metabolism Sex Factors

Journal

Nature metabolism
ISSN: 2522-5812
Titre abrégé: Nat Metab
Pays: Germany
ID NLM: 101736592

Informations de publication

Date de publication:
11 2021
Historique:
received: 14 09 2020
accepted: 17 09 2021
pubmed: 27 10 2021
medline: 4 1 2022
entrez: 26 10 2021
Statut: ppublish

Résumé

We have previously suggested a central role for mitochondria in the observed sex differences in metabolic traits. However, the mechanisms by which sex differences affect adipose mitochondrial function and metabolic syndrome are unclear. Here we show that in both mice and humans, adipose mitochondrial functions are elevated in females and are strongly associated with adiposity, insulin resistance and plasma lipids. Using a panel of diverse inbred strains of mice, we identify a genetic locus on mouse chromosome 17 that controls mitochondrial mass and function in adipose tissue in a sex- and tissue-specific manner. This locus contains Ndufv2 and regulates the expression of at least 89 mitochondrial genes in females, including oxidative phosphorylation genes and those related to mitochondrial DNA content. Overexpression studies indicate that Ndufv2 mediates these effects by regulating supercomplex assembly and elevating mitochondrial reactive oxygen species production, which generates a signal that increases mitochondrial biogenesis.

Identifiants

DOI: 10.1038/s42255-021-00481-w PMID: 34697471 PMC: PMC8909918
pubmed: 34697471
doi: 10.1038/s42255-021-00481-w
pii: 10.1038/s42255-021-00481-w
pmc: PMC8909918
mid: NIHMS1777029
doi:

Substances chimiques

Biomarkers 0
Reactive Oxygen Species 0
NADH Dehydrogenase EC 1.6.99.3
NDUFV2 protein, human EC 7.1.1.2

Types de publication

Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

1552-1568

Subventions

Organisme : NIDDK NIH HHS
ID : K99 DK120875
Pays : United States
Organisme : NHLBI NIH HHS
ID : R01 HL125863
Pays : United States
Organisme : NHLBI NIH HHS
ID : R01 HL147187
Pays : United States
Organisme : NHLBI NIH HHS
ID : R01 HL144651
Pays : United States
Organisme : NIDDK NIH HHS
ID : R01 DK117850
Pays : United States
Organisme : NHLBI NIH HHS
ID : P01 HL028481
Pays : United States
Organisme : NIDDK NIH HHS
ID : U54 DK120342
Pays : United States
Organisme : NIDDK NIH HHS
ID : P30 DK063491
Pays : United States
Organisme : NIAAA NIH HHS
ID : R01 AA026914
Pays : United States
Organisme : NCATS NIH HHS
ID : UL1 TR001881
Pays : United States
Organisme : NIDDK NIH HHS
ID : P30 DK041301
Pays : United States
Organisme : NIDDK NIH HHS
ID : R00 DK120875
Pays : United States

Informations de copyright

© 2021. The Author(s), under exclusive licence to Springer Nature Limited.

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Auteurs

Karthickeyan Chella Krishnan (K)

Department of Pharmacology and Systems Physiology, University of Cincinnati College of Medicine, Cincinnati, OH, USA. chellakn@ucmail.uc.edu.
Department of Medicine/Division of Cardiology, University of California, Los Angeles, CA, USA. chellakn@ucmail.uc.edu.
ORCID: 0000-0002-4895-2495

Laurent Vergnes (L)

Department of Human Genetics, University of California, Los Angeles, Los Angeles, CA, USA.

Rebeca Acín-Pérez (R)

Department of Medicine/Division of Endocrinology, University of California, Los Angeles, Los Angeles, CA, USA.

Linsey Stiles (L)

Department of Medicine/Division of Endocrinology, University of California, Los Angeles, Los Angeles, CA, USA.
Department of Molecular and Medical Pharmacology, University of California, Los Angeles, Los Angeles, CA, USA.
ORCID: 0000-0002-1514-458X

Michael Shum (M)

Department of Medicine/Division of Endocrinology, University of California, Los Angeles, Los Angeles, CA, USA.
Department of Molecular Medicine, Faculty of Medicine, Universite Laval, Quebec City, Quebec, Canada.
ORCID: 0000-0001-8784-9928

Lijiang Ma (L)

Department of Genetics and Genomic Sciences, The Icahn Institute for Genomics and Multiscale Biology, Icahn School of Medicine at Mount Sinai, New York, NY, USA.

Etienne Mouisel (E)

INSERM, UMR1297, Institute of Metabolic and Cardiovascular Diseases, University of Toulouse, Paul Sabatier University, Toulouse, France.

Calvin Pan (C)

Department of Human Genetics, University of California, Los Angeles, Los Angeles, CA, USA.
ORCID: 0000-0002-0752-833X

Timothy M Moore (TM)

Department of Medicine/Division of Cardiology, University of California, Los Angeles, CA, USA.
ORCID: 0000-0003-4250-3370

Miklós Péterfy (M)

Department of Medicine/Division of Cardiology, University of California, Los Angeles, CA, USA.
College of Osteopathic Medicine of the Pacific, Western University of Health Sciences, Pomona, CA, USA.

Casey E Romanoski (CE)

Department of Cellular and Molecular Medicine, University of Arizona, Tucson, AZ, USA.

Karen Reue (K)

Department of Human Genetics, University of California, Los Angeles, Los Angeles, CA, USA.
ORCID: 0000-0002-7487-2624

Johan L M Björkegren (JLM)

Department of Genetics and Genomic Sciences, The Icahn Institute for Genomics and Multiscale Biology, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
Integrated Cardio Metabolic Centre, Department of Medicine, Karolinska Institutet, Karolinska Universitetssjukhuset, Huddinge, Sweden.
ORCID: 0000-0003-1945-7425

Markku Laakso (M)

Institute of Clinical Medicine, Internal Medicine, University of Eastern Finland and Kuopio University Hospital, Kuopio, Finland.

Marc Liesa (M)

Department of Medicine/Division of Endocrinology, University of California, Los Angeles, Los Angeles, CA, USA.
Department of Molecular and Medical Pharmacology, University of California, Los Angeles, Los Angeles, CA, USA.
ORCID: 0000-0002-5909-8570

Aldons J Lusis (AJ)

Department of Medicine/Division of Cardiology, University of California, Los Angeles, CA, USA. jlusis@mednet.ucla.edu.
Department of Human Genetics, University of California, Los Angeles, Los Angeles, CA, USA. jlusis@mednet.ucla.edu.
Department of Microbiology, Immunology and Molecular Genetics, University of California, Los Angeles, Los Angeles, CA, USA. jlusis@mednet.ucla.edu.
ORCID: 0000-0001-9013-0228

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Classifications MeSH

questionsmedicales.fr › Tissus › Tissu conjonctif › Tissu adipeux › Sex-specific genetic regulation of adipose...
questionsmedicales.fr › Phénomènes physiologiques › Constitution physique › Composition corporelle › Répartition du tissu adipeux › Adiposité › Sex-specific genetic regulation of adipose...
questionsmedicales.fr › Eucaryotes › Animaux › Sex-specific genetic regulation of adipose...
questionsmedicales.fr › Facteurs biologiques › Marqueurs biologiques › Sex-specific genetic regulation of adipose...
questionsmedicales.fr › Phénomènes physiologiques cellulaires › Respiration cellulaire › Sex-specific genetic regulation of adipose...
questionsmedicales.fr › Phénomènes génétiques › Structures génétiques › Chromosomes › Chromosomes de mammifère › Chromosomes humains › Chromosomes humains 16-18 › Chromosomes humains de la paire 17 › Sex-specific genetic regulation of adipose...
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