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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)
Verlagsversion Preprint Forschungsdaten DOI PMC
Open Access Green möglich sobald Postprint bei der ZB eingereicht worden ist.
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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Publikationstyp Artikel: Journalartikel
Dokumenttyp Wissenschaftlicher Artikel
Korrespondenzautor
Schlagwörter 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
Zeitschrift Cell Metabolism
Quellenangaben Band: 29, Heft: 4, Seiten: 932-949.e4 Artikelnummer: , Supplement: ,
Verlag Elsevier
Verlagsort 50 Hampshire St, Floor 5, Cambridge, Ma 02139 Usa
Nichtpatentliteratur Publikationen
Begutachtungsstatus Peer reviewed
Institut(e) Research Unit Analytical Pathology (AAP)
Institute of Diabetes and Regeneration Research (IDR)