Effects of nicotinamide riboside supplementation on mitochondrial UPR in skeletal muscle and on aerobic performance of mice

Author(s)

Barbara Moreira Crisol

• Document type: Master's Dissertation
• Press: Limeira, SP.
• Institution: Universidade Estadual de Campinas (UNICAMP). Faculdade de Ciências Aplicadas
• Defense date: 2018-02-26

Examining board members

Eduardo Rochete Ropelle; Igor Luchini Baptista; Leonardo dos Reis Silveira

• Advisor: Eduardo Rochete Ropelle

Abstract

The molecule of Nicotinamide Adenine Nucleotide (NAD+) is extremely important for the control of metabolic homeostasis. The increase in NAD+ levels results in increased oxidative metabolism through the activation of SIRT1, and in two other processes related to mitochondrial activity, the unfolded protein response in the mitochondria (UPRmt) and the triggering of the mito-nuclear imbalance, which occurs when there is an imbalance in the protein content of mitochondrial proteins due to nuclear proteins. Studies show that supplementation with the NAD+ precursor, the Nicotinamide Riboside (NR), is capable to improve mitochondrial oxidative capacity and mitochondrial biogenesis through the activation of the UPRmt and the mito-nuclear imbalance in different tissues. In this sense, we hypothesized that NR supplementation could stimulate UPRmt and mito-nuclear imbalance in the skeletal muscles and thus increase aerobic performance. C57BL/ 6J mice were divided into the following groups: Control, NR supplementation, Chronic Exercise and Chronic Exercise + NR. Physiological assays were combined with biochemical and molecular assays for the evaluation of experimental groups. The results showed that the animals treated with NR alone, showed lower fat accumulation, increased heat production, increased muscle strength, and activation of the mitonuclear imbalance on the skeletal muscle. However, the supplementation by itself did not improved the animals¿ aerobic performance when compared to the no supplemented group. On the other hand, the animals from the Chronic exercise + NR group presented higher amount of type 1 fibers when compared to animals supplemented with NR alone or only exercised. In addition, trained and NR supplemented animals showed higher aerobic performance when compared to trained animals without supplementation. However, in a curious way, the combination Chronic Exercise + NR did not trigger the UPRmt or the mitonuclear imbalance in the skeletal muscles. We concluded that the combination of Chronic exercise + NR promoted important adaptations in the mouse skeletal muscle and a significant improvement in aerobic performance, however, this improvement was not associated to the activation of the UPRmt or the mitonuclear imbalance (AU)

• FAPESP's process: 16/05499-1 - Effects of nicotinamide Ribosoide supplementation on mitochondrial UPR in skeletal muscle and the aerobic performance of mice
• Grantee: Barbara Moreira Crisol
• Support Opportunities: Scholarships in Brazil - Master