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Systemic metabolite profiling reveals sexual dimorphism of AIBP control of metabolism in mice

Emerging studies indicate that APOA-I binding protein (AIBP) is a secreted protein and functions extracellularly to promote cellular cholesterol efflux, thereby disrupting lipid rafts on the plasma membrane. AIBP is also present in the mitochondria and acts as an epimerase, facilitating the repair o...

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Autores principales: Kim, Jun-dae, Zhu, Lingping, Sun, Quan, Fang, Longhou
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8016339/
https://www.ncbi.nlm.nih.gov/pubmed/33793635
http://dx.doi.org/10.1371/journal.pone.0248964
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author Kim, Jun-dae
Zhu, Lingping
Sun, Quan
Fang, Longhou
author_facet Kim, Jun-dae
Zhu, Lingping
Sun, Quan
Fang, Longhou
author_sort Kim, Jun-dae
collection PubMed
description Emerging studies indicate that APOA-I binding protein (AIBP) is a secreted protein and functions extracellularly to promote cellular cholesterol efflux, thereby disrupting lipid rafts on the plasma membrane. AIBP is also present in the mitochondria and acts as an epimerase, facilitating the repair of dysfunctional hydrated NAD(P)H, known as NAD(P)H(X). Importantly, AIBP deficiency contributes to lethal neurometabolic disorder, reminiscent of the Leigh syndrome in humans. Whereas cyclic NADPHX production is proposed to be the underlying cause, we hypothesize that an unbiased metabolic profiling may: 1) reveal new clues for the lethality, e.g., changes of mitochondrial metabolites., and 2) identify metabolites associated with new AIBP functions. To this end, we performed unbiased and profound metabolic studies of plasma obtained from adult AIBP knockout mice and control littermates of both genders. Our systemic metabolite profiling, encompassing 9 super pathways, identified a total of 640 compounds. Our studies demonstrate a surprising sexual dimorphism of metabolites affected by AIBP deletion, with more statistically significant changes in the AIBP knockout female vs male when compared with the corresponding controls. AIBP knockout trends to reduce cholesterol but increase the bile acid precursor 7-HOCA in female but not male. Complex lipids, phospholipids, sphingomyelin and plasmalogens were reduced, while monoacylglycerol, fatty acids and the lipid soluble vitamins E and carotene diol were elevated in AIBP knockout female but not male. NAD metabolites were not significantly different in AIBP knockout vs control mice but differed for male vs female mice. Metabolites associated with glycolysis and the Krebs cycle were unchanged by AIBP knockout. Importantly, polyamine spermidine, critical for many cellular functions including cerebral cortex synapses, was reduced in male but not female AIBP knockout. This is the first report of a systemic metabolite profile of plasma samples from AIBP knockout mice, and provides a metabolic basis for future studies of AIBP regulation of cellular metabolism and the pathophysiological presentation of AIBP deficiency in patients.
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spelling pubmed-80163392021-04-08 Systemic metabolite profiling reveals sexual dimorphism of AIBP control of metabolism in mice Kim, Jun-dae Zhu, Lingping Sun, Quan Fang, Longhou PLoS One Research Article Emerging studies indicate that APOA-I binding protein (AIBP) is a secreted protein and functions extracellularly to promote cellular cholesterol efflux, thereby disrupting lipid rafts on the plasma membrane. AIBP is also present in the mitochondria and acts as an epimerase, facilitating the repair of dysfunctional hydrated NAD(P)H, known as NAD(P)H(X). Importantly, AIBP deficiency contributes to lethal neurometabolic disorder, reminiscent of the Leigh syndrome in humans. Whereas cyclic NADPHX production is proposed to be the underlying cause, we hypothesize that an unbiased metabolic profiling may: 1) reveal new clues for the lethality, e.g., changes of mitochondrial metabolites., and 2) identify metabolites associated with new AIBP functions. To this end, we performed unbiased and profound metabolic studies of plasma obtained from adult AIBP knockout mice and control littermates of both genders. Our systemic metabolite profiling, encompassing 9 super pathways, identified a total of 640 compounds. Our studies demonstrate a surprising sexual dimorphism of metabolites affected by AIBP deletion, with more statistically significant changes in the AIBP knockout female vs male when compared with the corresponding controls. AIBP knockout trends to reduce cholesterol but increase the bile acid precursor 7-HOCA in female but not male. Complex lipids, phospholipids, sphingomyelin and plasmalogens were reduced, while monoacylglycerol, fatty acids and the lipid soluble vitamins E and carotene diol were elevated in AIBP knockout female but not male. NAD metabolites were not significantly different in AIBP knockout vs control mice but differed for male vs female mice. Metabolites associated with glycolysis and the Krebs cycle were unchanged by AIBP knockout. Importantly, polyamine spermidine, critical for many cellular functions including cerebral cortex synapses, was reduced in male but not female AIBP knockout. This is the first report of a systemic metabolite profile of plasma samples from AIBP knockout mice, and provides a metabolic basis for future studies of AIBP regulation of cellular metabolism and the pathophysiological presentation of AIBP deficiency in patients. Public Library of Science 2021-04-01 /pmc/articles/PMC8016339/ /pubmed/33793635 http://dx.doi.org/10.1371/journal.pone.0248964 Text en © 2021 Kim et al http://creativecommons.org/licenses/by/4.0/ This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
spellingShingle Research Article
Kim, Jun-dae
Zhu, Lingping
Sun, Quan
Fang, Longhou
Systemic metabolite profiling reveals sexual dimorphism of AIBP control of metabolism in mice
title Systemic metabolite profiling reveals sexual dimorphism of AIBP control of metabolism in mice
title_full Systemic metabolite profiling reveals sexual dimorphism of AIBP control of metabolism in mice
title_fullStr Systemic metabolite profiling reveals sexual dimorphism of AIBP control of metabolism in mice
title_full_unstemmed Systemic metabolite profiling reveals sexual dimorphism of AIBP control of metabolism in mice
title_short Systemic metabolite profiling reveals sexual dimorphism of AIBP control of metabolism in mice
title_sort systemic metabolite profiling reveals sexual dimorphism of aibp control of metabolism in mice
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8016339/
https://www.ncbi.nlm.nih.gov/pubmed/33793635
http://dx.doi.org/10.1371/journal.pone.0248964
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