Transcriptional response of white adipose tissue to withdrawal of vitamin B3

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Shi W, Hegeman MA, van der Stelt I, Bekkenkamp-Grovenstein M, van Schothorst EM, Brenner C, de Boer VCJ, Keijer J

Abstract

Journal

Molecular Nutrition & Food Research

Model

Mouse

Impact Factor

5.151

Scope

Distinct markers for mild vitamin B3 deficiency are lacking. To identify these, we examined the molecular responses of white adipose tissue (WAT) to vitamin B3 withdrawal.

Methods and Results

A dietary intervention was performed in male C57BL/6JRccHsd mice, in which a diet without nicotinamide riboside (NR) was compared to a diet with NR at the recommended vitamin B3 level. Both diets contained low but adequate level of tryptophan. Metabolic flexibility and systemic glucose tolerance were analysed and global transcriptomics, qRT-PCR and histology of epididymal WAT (eWAT) were performed. We observed a decreased insulin sensitivity and a shift from carbohydrate to fatty acid oxidation in response to vitamin B3 withdrawal. This was consistent with molecular changes in eWAT, including an activated MEK/ERK signalling, a lowering of glucose utilization markers and an increase in makers of fatty acid catabolism, possibly related to the consistent lower expression of mitochondrial electron transport complexes. The synthesis pathway of tetrahydropteridine (BH4), an essential cofactor for neurotransmitter synthesis, was transcriptionally activated. Genes marking these processes were technically validated.

Conclusions

We propose the downregulation of Anp32a,Tnk2 and the upregulation of Mapk1, Map2k1, Qdpr, Mthfs, and Mthfsl as a WAT transcriptional signature marker for mild vitamin B3 deficiency. This article is protected by copyright. All rights reserved.

Keywords

MEK/ERK; biomarkers; deficiency; tetrahydropteridine; vitamin B3

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