@article{3fd9d8ab921c4a09be006fce6062d302,
title = "Sex-specific genetic regulation of adipose mitochondria and metabolic syndrome by Ndufv2",
abstract = "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.",
author = "{Chella Krishnan}, Karthickeyan and Laurent Vergnes and Rebeca Ac{\'i}n-P{\'e}rez and Linsey Stiles and Michael Shum and Lijiang Ma and Etienne Mouisel and Calvin Pan and Moore, {Timothy M.} and Mikl{\'o}s P{\'e}terfy and Romanoski, {Casey E.} and Karen Reue and Bj{\"o}rkegren, {Johan L.M.} and Markku Laakso and Marc Liesa and Lusis, {Aldons J.}",
note = "Funding Information: We thank Z. Zhou, Y. Meng, S. Charugundla, D. W. Jayasekera, S. Nand and J. Ure for assistance in experiments. This work was supported by NIH grants NIH-P01HL028481, NIH-R01DK117850 and NIH-R01HL144651 (A.J.L.), NIH-R01HL125863 (J.L.M.B.), NIH-R01HL147187 (C.E.R.), NIH-1R01AA026914-01A1 (M. Liesa), NIH-R00DK120875 (K.C.K) and NIH-K99DK120875 (K.C.K); UCLA/UCSD/CTSI grants P30DK41301 (M. Liesa), UL1TR001881 (M. Liesa), P30DK063491 (M. Liesa); the American Heart Association grants A14SFRN20840000 (J.L.M.B.) and 18POST33990256 (K.C.K.); the Academy of Finland 321428 (M. Laakso); the Swedish Research Council 2018-02529 (J.L.M.B); Heart Lung Foundation 20170265 (J.L.M.B.); Astra-Zeneca through ICMC, Karolinska Institutet, Sweden (J.L.M.B.) and the Foundation Leducq 12CVD04 (L.V. and K.R.) and 18CVD02 (J.L.M.B.). The funders had no role in the study design, data collection and interpretation, or the decision to submit the work for publication. Publisher Copyright: {\textcopyright} 2021, The Author(s), under exclusive licence to Springer Nature Limited.",
year = "2021",
month = nov,
doi = "10.1038/s42255-021-00481-w",
language = "English (US)",
volume = "3",
pages = "1552--1568",
journal = "Nature Metabolism",
issn = "2522-5812",
publisher = "Springer Berlin",
number = "11",
}