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Limiting Mrs2-Dependent Mg2+ Uptake Induces Metabolic Programming in Prolonged Dietary Stress

ABSTRACT: MANUSCRIPT ABSTRACT: The most abundant cellular divalent cations, Mg2+ (mM) and Ca2+ (nM-µM), antagonistically regulate divergent metabolic pathways with several orders of magnitude affinity preference, but its physiological significance of this competition remains largely unknown. In mice consuming a Western diet, genetic ablation of the mitochondrial Mg2+ channel Mrs2 prevents weight gain, enhances mitochondrial activity, decreases fat accumulation in the liver, and causes prominent browning of white adipose. Mrs2 deficiency further restrains citrate efflux from the mitochondria, making it unavailable to support de novo lipogenesis. As citrate is an endogenous Mg2+ chelator, this may represent an adaptive response to a perceived deficit of the cation. Transcriptional profiling of liver and white adipose reveals higher expression of genes involved in glycolysis, b-oxidation, thermogenesis, and HIF-1a-targets, in Mrs2-/- mice that are further enhanced under Western diet-associated metabolic stress. Thus, lowering mMg2+ is sufficient to promote metabolism and dampens diet induced obesity and metabolic syndrome.

ORGANISM(S): Mus musculus

PROVIDER: GSE216538 | GEO | 2023/05/03

REPOSITORIES: GEO

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