| Literature DB >> 30639359 |
Frode Norheim1, Yehudit Hasin-Brumshtein2, Laurent Vergnes3, Karthickeyan Chella Krishnan2, Calvin Pan2, Marcus M Seldin2, Simon T Hui2, Margarete Mehrabian2, Zhiqiang Zhou2, Sonul Gupta2, Brian W Parks4, Axel Walch5, Karen Reue3, Susanna M Hofmann6, Arthur P Arnold7, Aldons J Lusis8.
Abstract
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-by-sex 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 mitochondrial 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.Entities:
Keywords: adipose tissue “browning”; gene-by-sex interactions; gonadectomy; hybrid mouse diversity panel; mitochondrial functions; sex differences; uncoupling protein-1
Mesh：
Year: 2019 PMID： 30639359 PMCID： PMC6447452 DOI： 10.1016/j.cmet.2018.12.013
Source DB: PubMed Journal: Cell Metab ISSN： 1550-4131 Impact factor: 27.287