Results
Title

Evidence for a Direct Effect of the NAD<sup> </sup> Precursor Acipimox on Muscle Mitochondrial Function in Humans.

Authors

van de Weijer, Tineke; Phielix, Esther; Bilet, Lena; Williams, Evan G.; Ropelle, Eduardo R.; Bierwagen, Alessandra; Livingstone, Roshan; Nowotny, Peter; Sparks, Lauren M.; Paglialunga, Sabina; Szendroedi, Julia; Havekes, Bas; Moullan, Norman; Pirinen, Eija; Jong-Hee Hwang; Schrauwen-Hinderling, Vera B.; Hesselink, Matthijs K. C.; Auwerx, Johan; Roden, Michael; Schrauwen, Patrick

Abstract

Recent preclinical studies showed the potential of nicotinamide adenine dinucleotide (NAD ) precursors to increase oxidative phosphorylation and improve metabolic health, but human data are lacking. We hypothesize that the nicotinic acid derivative acipimox, an NAD precursor, would directly affect mitochondrial function independent of reductions in nonesterified fatty acid (NEFA) concentrations. In a multicenter randomized crossover trial, 21 patients with type 2 diabetes (age 57.7 ± 1.1 years, BMI 33.4 ± 0.8 kg/m ²) received either placebo or acipimox 250 mg three times daily dosage for 2 weeks. Acipimox treatment increased plasma NEFA levels (759 ± 44 vs. 1,135 ± 97 μmol/L for placebo vs. acipimox, P levels, mitonuclear protein imbalance, and mitochondrial oxidative capacity. To the best of our knowledge, this study is the first to demonstrate that NAD boosters can also directly affect skeletal muscle mitochondrial function in humans.

Subjects

MUSCLE mitochondria; MITOCHONDRIA; NICOTINAMIDE; AMIDES; NIACIN

Publication

Diabetes, 2015, Vol 64, Issue 4, p1193

ISSN

0012-1797

Publication type

Academic Journal

DOI

10.2337/db14-0667