Transcriptional Response of White Adipose Tissue to Withdrawal of Vitamin B3

Wenbiao Shi, Maria A. Hegeman, Atanaska Doncheva, Inge van der Stelt, Melissa Bekkenkamp‐Grovenstein, Evert M. van Schothorst, Charles Brenner, Vincent C.J. Boer, Jaap Keijer*

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

1 Citation (Scopus)

Abstract

SCOPE: Distinct markers for mild vitamin B3 deficiency are lacking. To identify these, the molecular responses of white adipose tissue (WAT) to vitamin B3 withdrawal are examined.
METHODS AND RESULTS: A dietary intervention is performed in male C57BL/6JRccHsd mice, in which a diet without nicotinamide riboside (NR) is compared to a diet with NR at the recommended vitamin B3 level. Both diets contain low but adequate level of tryptophan. Metabolic flexibility and systemic glucose tolerance are analyzed and global transcriptomics, qRT-PCR, and histology of epididymal WAT (eWAT) are performed. A decreased insulin sensitivity and a shift from carbohydrate to fatty acid oxidation in response to vitamin B3 withdrawal are observed. This is consistent with molecular changes in eWAT, including an activated MEK/ERK signaling, 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, is transcriptionally activated. Genes marking these processes are technically validated.
CONCLUSION: The downregulation of Anp32a, Tnk2 and the upregulation of Mapk1, Map2k1, Qdpr, Mthfs, and Mthfsl are proposed as a WAT transcriptional signature marker for mild vitamin B3 deficiency
Original languageEnglish
Article numbere1801100
JournalMolecular Nutrition & Food Research
DOIs
Publication statusE-pub ahead of print - 16 Apr 2019

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