The impact of chromosomal sex on cardiometabolic health and disease

Wiese, Carrie B.; Avetisyan, Rozeta; Reue, Karen

doi:10.1016/j.tem.2023.07.003

Trends in Endocrinology & Metabolism

2023

DOI: 10.1016/j.tem.2023.07.003

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The impact of chromosomal sex on cardiometabolic health and disease

Carrie B. Wiese,

Rozeta Avetisyan,

Karen Reue

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2024

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Cited by 6 publications

(1 citation statement)

References 101 publications

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“…Mechanisms that influence sex differences in adiposity include both gonadal hormones (from ovaries or testes) and chromosomal sex (XX or XY chromosomes) [ 5 ]. Ovarian hormones have a major impact on fat storage, as established by studies in pre- and postmenopausal women, and in rodents before and after removal of gonads.…”

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confidence: 99%

Gene Regulation and Mitochondrial Activity During White and Brown Adipogenesis Are Modulated by KDM5 Histone Demethylase

Vergnes,

Wiese,

Zore

et al. 2024

Journal of the Endocrine Society

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Body fat accumulation differs between males and females and is influenced by both gonadal sex (ovaries vs. testes) and chromosomal sex (XX vs. XY). We previously showed that an X chromosome gene, Kdm5c, is expressed at higher levels in females compared to males and correlates with adiposity in mice and humans. Kdm5c encodes a KDM5 histone demethylase that regulates gene expression by modulating histone methylation at gene promoters and enhancers. Here, we use chemical inhibition and genetic knockdown to identify a role for KDM5 activity during early stages of white and brown preadipocyte differentiation, with specific effects on white adipocyte clonal expansion, and white and brown adipocyte gene expression and mitochondrial activity. In white adipogenesis, KDM5 activity modulates H3K4 histone methylation at the Dlk1 gene promoter to repress gene expression and promote progression from preadipocytes to mature adipocytes. In brown adipogenesis, KDM5 activity modulates H3K4 methylation and gene expression of Ucp1, which is required for thermogenesis. Unbiased transcriptome analysis revealed that KDM5 activity regulates genes associated with cell cycle regulation and mitochondrial function, and this was confirmed by functional analyses of cell proliferation and cellular bioenergetics. Using genetic knockdown, we demonstrate that KDM5C is the likely KDM5 family member that is responsible for regulation of white and brown preadipocyte programming. Given that KDM5C levels are higher in females compared to males, our findings suggest that sex differences in white and brown preadipocyte gene regulation may contribute to sex differences in adipose tissue function.

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confidence: 99%

Gene Regulation and Mitochondrial Activity During White and Brown Adipogenesis Are Modulated by KDM5 Histone Demethylase

Vergnes,

Wiese,

Zore

et al. 2024

Journal of the Endocrine Society

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Glia dysfunction in schizophrenia: evidence of possible therapeutic effects of nervonic acid in a preclinical model

Wang,

Fu,

Wang

et al. 2024

Psychopharmacology

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Régulation du chromosome X et spécificités fonctionnelles des cellules femelles

Chaumeil,

Morey

2024

Med Sci (Paris)

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Et si posséder deux chromosomes X conférait aux cellules femelles des spécificités exclusives et expliquait les différences de susceptibilité des hommes et des femmes à certaines maladies ? Pourtant, l’un des chromosomes X est réprimé aléatoirement dans chaque cellule femelle dès le stade embryonnaire, ce qui, théoriquement, remet les sexes à égalité. Cette inactivation du chromosome X est un processus épigénétique unique : elle agit à l’échelle d’un chromosome entier et aboutit à un mosaïcisme d’expression des gènes du chromosome X au niveau de l’organisme. Cependant certains gènes échappent au processus et cette inactivation semble être plus labile dans certains types cellulaires. Quelles en sont les conséquences physiologiques ? Cette question commence à être explorée, notamment dans les systèmes immunitaires et nerveux qui présentent différentes maladies à biais de sexe.

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The impact of chromosomal sex on cardiometabolic health and disease

Cited by 6 publications

References 101 publications

Gene Regulation and Mitochondrial Activity During White and Brown Adipogenesis Are Modulated by KDM5 Histone Demethylase

Gene Regulation and Mitochondrial Activity During White and Brown Adipogenesis Are Modulated by KDM5 Histone Demethylase

Glia dysfunction in schizophrenia: evidence of possible therapeutic effects of nervonic acid in a preclinical model

Régulation du chromosome X et spécificités fonctionnelles des cellules femelles

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