Sex-specific genetic regulation of adipose mitochondria and metabolic syndrome by Ndufv2.

Autor:	Chella Krishnan K; Department of Pharmacology and Systems Physiology, University of Cincinnati College of Medicine, Cincinnati, OH, USA. chellakn@ucmail.uc.edu.; Department of Medicine/Division of Cardiology, University of California, Los Angeles, CA, USA. chellakn@ucmail.uc.edu., Vergnes L; Department of Human Genetics, University of California, Los Angeles, Los Angeles, CA, USA., Acín-Pérez R; Department of Medicine/Division of Endocrinology, University of California, Los Angeles, Los Angeles, CA, USA., Stiles L; Department of Medicine/Division of Endocrinology, University of California, Los Angeles, Los Angeles, CA, USA.; Department of Molecular and Medical Pharmacology, University of California, Los Angeles, Los Angeles, CA, USA., Shum M; Department of Medicine/Division of Endocrinology, University of California, Los Angeles, Los Angeles, CA, USA.; Department of Molecular Medicine, Faculty of Medicine, Universite Laval, Quebec City, Quebec, Canada., Ma L; Department of Genetics and Genomic Sciences, The Icahn Institute for Genomics and Multiscale Biology, Icahn School of Medicine at Mount Sinai, New York, NY, USA., Mouisel E; INSERM, UMR1297, Institute of Metabolic and Cardiovascular Diseases, University of Toulouse, Paul Sabatier University, Toulouse, France., Pan C; Department of Human Genetics, University of California, Los Angeles, Los Angeles, CA, USA., Moore TM; Department of Medicine/Division of Cardiology, University of California, Los Angeles, CA, USA., Péterfy M; Department of Medicine/Division of Cardiology, University of California, Los Angeles, CA, USA.; College of Osteopathic Medicine of the Pacific, Western University of Health Sciences, Pomona, CA, USA., Romanoski CE; Department of Cellular and Molecular Medicine, University of Arizona, Tucson, AZ, USA., Reue K; Department of Human Genetics, University of California, Los Angeles, Los Angeles, CA, USA., Björkegren JLM; Department of Genetics and Genomic Sciences, The Icahn Institute for Genomics and Multiscale Biology, Icahn School of Medicine at Mount Sinai, New York, NY, USA.; Integrated Cardio Metabolic Centre, Department of Medicine, Karolinska Institutet, Karolinska Universitetssjukhuset, Huddinge, Sweden., Laakso M; Institute of Clinical Medicine, Internal Medicine, University of Eastern Finland and Kuopio University Hospital, Kuopio, Finland., Liesa M; Department of Medicine/Division of Endocrinology, University of California, Los Angeles, Los Angeles, CA, USA.; Department of Molecular and Medical Pharmacology, University of California, Los Angeles, Los Angeles, CA, USA., Lusis AJ; Department of Medicine/Division of Cardiology, University of California, Los Angeles, CA, USA. jlusis@mednet.ucla.edu.; Department of Human Genetics, University of California, Los Angeles, Los Angeles, CA, USA. jlusis@mednet.ucla.edu.; Department of Microbiology, Immunology and Molecular Genetics, University of California, Los Angeles, Los Angeles, CA, USA. jlusis@mednet.ucla.edu.
Jazyk:	angličtina
Zdroj:	Nature metabolism [Nat Metab] 2021 Nov; Vol. 3 (11), pp. 1552-1568. Date of Electronic Publication: 2021 Oct 25.
DOI:	10.1038/s42255-021-00481-w
Abstrakt:	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. (© 2021. The Author(s), under exclusive licence to Springer Nature Limited.)
Databáze:	MEDLINE
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