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Norheim, F.* ; Hasin-Brumshtein, Y.* ; Vergnes, L.* ; Chella Krishnan, K.* ; Pan, C.* ; Seldin, M.M.* ; Hui, S.T.* ; Mehrabian, M.* ; Zhou, Z.* ; Gupta, S.* ; Parks, B.W.* ; Walch, A.K. ; Reue, K.* ; Hofmann, S.M. ; Arnold, A.P.* ; Lusis, A.J.*

Gene-by-sex interactions in mitochondrial functions and cardio-metabolic traits.

Cell Metab. 29, 932-949.e4 (2019)
Publ. Version/Full Text Preprint Research data DOI
Open Access Green as soon as Postprint is submitted to ZB.
We studied sex differences in over 50 cardio-metabolic traits in a panel of 100 diverse inbred strains of mice. The results clearly showed that the effects of sex on both clinical phenotypes and gene expression depend on the genetic background. In support of this, genetic loci associated with the traits frequently showed sex specificity. For example, Lyplal1, a gene implicated in human obesity, was shown to underlie a sex-specific locus for diet induced obesity. Global gene expression analyses of tissues across the panel implicated adipose tissue "beiging" and mitochondrial functions in the sex differences. Isolated mitochondria showed gene-bysex interactions in oxidative functions, such that some strains (C57BL/6J) showed similar function between sexes, whereas others (DBA/2J and A/J) showed increased function in females. Reduced adipose mitochondria! function in males as compared to females was associated with increased susceptibility to obesity and insulin resistance. Gonadectomy studies indicated that gonadal hormones acting in a tissue-specific manner were responsible in part for the sex differences.
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Publication type Article: Journal article
Document type Scientific Article
Keywords Adipose Tissue “browning” ; Gene-by-sex Interactions ; Gonadectomy ; Hybrid Mouse Diversity Panel ; Mitochondrial Functions ; Sex Differences ; Uncoupling Protein-1; Genome-wide Association; Gut Microbiota Composition; Brown Adipose-tissue; Systems Genetics; High-fat; Expression; Dimorphism; Loci; Inflammation; Architecture
ISSN (print) / ISBN 1550-4131
e-ISSN 1932-7420
Journal Cell Metabolism
Quellenangaben Volume: 29, Issue: 4, Pages: 932-949.e4 Article Number: , Supplement: ,
Publisher Elsevier
Publishing Place 50 Hampshire St, Floor 5, Cambridge, Ma 02139 Usa
Reviewing status Peer reviewed