Ole Dollerup - Defining the Molecular Networks Responsible for the Insulin Sensitizing Effects of Nicotinamide Riboside in Humans

The overall objective of this PhD project is to define the molecular networks responsible for the putative changes in insulin sensitivity in human skeletal muscle in response to treatment with nicotinamide riboside (NR), a member of the vitamin B3 family with potent effects on metabolism in cell culture systems and rodents.

NR treatment increases intracellular nicotinamide adenine dinucleotide (NAD) levels in rodent models concurrent with enhanced activity of NAD-dependent sirtuins. The current hypothesis in the field is that increased sirtuin-mediated deacetylation of transcription factors and mitochondrial proteins involved in ATP synthesis increase fat oxidation and improve insulin sensitivity.

In this proposal we will employ state-of-the-art methodologies to determine if treatment can improve insulin sensitivity, substrate metabolism, body composition, and gut microbiota in obese, non-diabetic humans, alone and in combination with endurance exercise training. Furthermore, we aim to define the molecular networks in skeletal muscle and adipose tissue responsible for the putative beneficial effects of NR using highly sensitive mass spectrometry-based metabolomic and proteomic analyses.

This will be the first human clinical trial investigating long-term effects of NR supplementation on insulin sensitivity, and the potential role of NR as a future anti-diabetic drug.ng Effects of Nicotinamide Riboside in Humans