Nicotinamide riboside supplementation dysregulates redox and energy metabolism in rats: Implications for exercise performance

New Findings: What is the central question of this study? The aim was to investigate the potential metabolic and redox mechanisms that impaired exercise performance after 21 days of supplementation with 300 mg (kg body weight)−1 of nicotinamide riboside in rats. What is the main finding and its importance? Nicotinamide riboside disturbed energy and redox metabolism and impaired exercise performance in heathy rats. Exogenously administered redox agents in heathy populations might lead to adverse effects. Abstract: Nicotinamide riboside is a recently discovered form of vitamin B3 that can increase NAD(P) levels. NAD(P) plays key roles in energy metabolism, and its main function is the transfer of electrons in various cellular reactions. Research in aged or diseased mice reported that nicotinamide riboside increases NAD(H) levels, reduces morbidity and improves health and muscle function. We have recently shown that in healthy young rats, chronic administration of nicotinamide riboside marginally non-significantly decreased exercise performance by 35% (P = 0.071). As a follow-up to this finding, we analysed samples from these animals, in an attempt to reveal the potential mechanisms driving this adverse effect, focusing on redox homeostasis and bioenergetics. Thirty-eight Wistar rats were divided into four groups: control (n = 10), exercise (n = 9), nicotinamide riboside (n = 10) and exercise plus nicotinamide riboside (n = 9). Nicotinamide riboside was administered for 21 days [300 mg (kg body weight)−1 daily]. At the end of administration, the exercise and the exercise plus nicotinamide riboside groups performed an incremental swimming performance test until exhaustion. Nicotinamide riboside supplementation increased the levels of NADPH in the liver (P = 0.050), increased the levels of F2-isoprostanes in plasma (P = 0.047), decreased the activity of glutathione peroxidase (P = 0.017), glutathione reductase (P < 0.001) and catalase (P = 0.024) in erythrocytes, increased the level of glycogen in the liver (P < 0.001) and decreased the concentration of glucose (P = 0.016) and maximal lactate accumulation in plasma (P = 0.084). These findings support the prevailing idea that exogenously administered redox agents in heathy populations might lead to adverse effects and not necessarily to beneficial or neutral effects. © 2018 The Authors. Experimental Physiology © 2018 The Physiological Societ

Nicotinamide riboside supplementation dysregulates redox and energy metabolism in rats: Implications for exercise performance

New Findings: What is the central question of this study? The aim was to investigate the potential metabolic and redox mechanisms that impaired exercise performance after 21 days of supplementation with 300 mg (kg body weight)−1 of nicotinamide riboside in rats. What is the main finding and its importance? Nicotinamide riboside disturbed energy and redox metabolism and impaired exercise performance in heathy rats. Exogenously administered redox agents in heathy populations might lead to adverse effects. Abstract: Nicotinamide riboside is a recently discovered form of vitamin B3 that can increase NAD(P) levels. NAD(P) plays key roles in energy metabolism, and its main function is the transfer of electrons in various cellular reactions. Research in aged or diseased mice reported that nicotinamide riboside increases NAD(H) levels, reduces morbidity and improves health and muscle function. We have recently shown that in healthy young rats, chronic administration of nicotinamide riboside marginally non-significantly decreased exercise performance by 35% (P = 0.071). As a follow-up to this finding, we analysed samples from these animals, in an attempt to reveal the potential mechanisms driving this adverse effect, focusing on redox homeostasis and bioenergetics. Thirty-eight Wistar rats were divided into four groups: control (n = 10), exercise (n = 9), nicotinamide riboside (n = 10) and exercise plus nicotinamide riboside (n = 9). Nicotinamide riboside was administered for 21 days [300 mg (kg body weight)−1 daily]. At the end of administration, the exercise and the exercise plus nicotinamide riboside groups performed an incremental swimming performance test until exhaustion. Nicotinamide riboside supplementation increased the levels of NADPH in the liver (P = 0.050), increased the levels of F2-isoprostanes in plasma (P = 0.047), decreased the activity of glutathione peroxidase (P = 0.017), glutathione reductase (P < 0.001) and catalase (P = 0.024) in erythrocytes, increased the level of glycogen in the liver (P < 0.001) and decreased the concentration of glucose (P = 0.016) and maximal lactate accumulation in plasma (P = 0.084). These findings support the prevailing idea that exogenously administered redox agents in heathy populations might lead to adverse effects and not necessarily to beneficial or neutral effects. © 2018 The Authors. Experimental Physiology © 2018 The Physiological Societ

Olive oil with high polyphenolic content induces both beneficial and harmful alterations on rat redox status depending on the tissue

Olive oil (OO) possesses a predominant role in the diet of Mediterranean countries. According to a health claim approved by the European Food Safety Authority, OO protects against oxidative stress‑induced lipid peroxidation in human blood, when it contains at least 5 mg of hydroxytyrosol and its derivatives per 20 g. However, studies regarding the effects of a total OO biophenols on redox status in vivo are scarce and either observational and do not provide a holistic picture of their action in tissues. Following a series of in vitro screening tests an OO containing biophenols at 800 mg/kg of OO was administered for 14 days to male Wistar rats at a dose corresponding to 20 g OO/per day to humans. Our results showed that OO reinforced the antioxidant profile of blood, brain, muscle and small intestine, it induced oxidative stress in spleen, pancreas, liver and heart, whereas no distinct effects were observed in lung, colon and kidney. The seemingly negative effects of OO follow the recently formulated idea in toxicology, namely the real life exposure scenario. This study reports that OO, although considered a nutritional source rich in antioxidants, it exerts a tissues specific action when administered in vivo. © 2020 The Author

Saccharomyces cerevisiae Ccr4–Not complex contributes to the control of Msn2p-dependent transcription by the Ras/cAMP pathway

The Ccr4–Not complex is a global regulator of transcription that affects genes positively and negatively and is thought to modulate the activity of TFIID. In the present work, we provide evidence that the Ccr4–Not complex may contribute to transcriptional regulation by the Ras/cAMP pathway. Several observations support this model. First, Msn2/4p-dependent transcription, which is known to be under negative control of cAMP-dependent protein kinase (PKA), is derepressed in all ccr4–not mutants. This phenotype is paralleled by specific post-translational modification defects of Msn2p in ccr4–not mutants relative to wild-type cells. Secondly, mutations in various NOT genes result in a synthetic temperature-sensitive growth defect when combined with mutations that compromise cells for PKA activity and at least partially suppress the effects of both a dominant-active RAS2Val-19 allele and loss of Rim15p. Thirdly, Not3p and Not5p, which are modified and subsequently degraded by stress signals that also lead to increased Msn2/4p-dependent activity, show a specific twohybrid interaction with Tpk2p. Together, our results suggest that the Ccr4–Not complex may function as an effector of the Ras/cAMP pathway that contributes to repress basal, stress- and starvation-induced transcription by Msn2/4p