The white adipose tissue transcriptional response to withdrawal of vitamin B3

Distinct markers for early, mild vitamin B3 deficiency are lacking. To identify these, we examined the molecular responses of white adipose tissue to vitamin B3 withdrawal. We performed a dietary intervention in male C57Bl/6JRcc mice. A diet with a low but adequate level of tryptophan without nicotinamide riboside (NR) was compared to the same diet with NR at the recommended vitamin B3 (30 mg NR per kg diet). Physiological and circulating parameters were determined and global transcriptomics, qRT-PCR and histology of epididymal white adipose tissue (eWAT) were done. We observed a decreased insulin sensitivity and a shift from carbohydrate to fatty acid oxidation. This was consistent with molecular changes in eWAT, where we observed an altered MEK/ERK signalling, a lowering of glucose utilization markers and an increase in makers of fatty acid catabolism, which may be related to the consistent reduction of mitochondrial OXPHOS Complex I (mRNAs and protein). The synthesis pathway of tetrahydropteridine (BH4), an essential cofactor for neurotransmitter synthesis, was found to be increased. Based on our results, we propose the technically validated downregulation of Anp32a, Tnk2 and the upregulation of Mapk1, Map2k1, Mthfs, Mthfsl and Qdpr as a WAT transcriptional signature marker for mild vitamin B3 deficiency