NAD+ and NAFLD - Caution, Causality, and Careful Optimism
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NAD+ and NAFLD - Caution, Causality, and Careful Optimism. / Dall, Morten; Hassing, Anna S; Treebak, Jonas T.
In: The Journal of Physiology, Vol. 600, No. 5, 2022, p. 1135-1154.Research output: Contribution to journal › Journal article › peer-review
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TY - JOUR
T1 - NAD+ and NAFLD - Caution, Causality, and Careful Optimism
AU - Dall, Morten
AU - Hassing, Anna S
AU - Treebak, Jonas T
N1 - This article is protected by copyright. All rights reserved.
PY - 2022
Y1 - 2022
N2 - The prevalence of non-alcoholic fatty liver disease (NAFLD) is increasing worldwide, and new treatments are direly needed. Nicotinamide adenine dinucleotide (NAD+ ) has been proposed as a potential target to prevent and reverse NAFLD. NAD+ is an important redox factor for energy metabolism and is used as a substrate by a range of enzymes, including sirtuins (SIRT), which regulates histone acetylation, transcription factor activity and mitochondrial function. NAD+ is also a precursor for reduced nicotinamide adenine dinucleotide phosphate (NADPH), which is an important component of the antioxidant defense system. NAD+ precursors such as nicotinamide riboside (NR) and nicotinamide mononucleotide (NMN) are available as over-the-counter dietary supplements, and oral supplementation with these precursors increases hepatic NAD+ levels and prevent hepatic lipid accumulation in pre-clinical models of NAFLD. Moreover, NAD+ precursors were found to improve hepatic mitochondrial function and decrease oxidative stress in pre-clinical NAFLD models. NAD+ repletion also prevents NAFLD progression to non-alcoholic steatohepatitis (NASH), as NAD+ precursor supplementation is associated with decreased hepatic stellate cell activation, and decreased fibrosis. However, initial clinical trials have only shown modest effects when NAD+ precursors were administrated to people with obesity. We review the available pre-clinical investigations of NAD+ supplementation for targeting NAFLD, and discuss how data from the first clinical trials can be reconciled with observations from preclinical research. This article is protected by copyright. All rights reserved.
AB - The prevalence of non-alcoholic fatty liver disease (NAFLD) is increasing worldwide, and new treatments are direly needed. Nicotinamide adenine dinucleotide (NAD+ ) has been proposed as a potential target to prevent and reverse NAFLD. NAD+ is an important redox factor for energy metabolism and is used as a substrate by a range of enzymes, including sirtuins (SIRT), which regulates histone acetylation, transcription factor activity and mitochondrial function. NAD+ is also a precursor for reduced nicotinamide adenine dinucleotide phosphate (NADPH), which is an important component of the antioxidant defense system. NAD+ precursors such as nicotinamide riboside (NR) and nicotinamide mononucleotide (NMN) are available as over-the-counter dietary supplements, and oral supplementation with these precursors increases hepatic NAD+ levels and prevent hepatic lipid accumulation in pre-clinical models of NAFLD. Moreover, NAD+ precursors were found to improve hepatic mitochondrial function and decrease oxidative stress in pre-clinical NAFLD models. NAD+ repletion also prevents NAFLD progression to non-alcoholic steatohepatitis (NASH), as NAD+ precursor supplementation is associated with decreased hepatic stellate cell activation, and decreased fibrosis. However, initial clinical trials have only shown modest effects when NAD+ precursors were administrated to people with obesity. We review the available pre-clinical investigations of NAD+ supplementation for targeting NAFLD, and discuss how data from the first clinical trials can be reconciled with observations from preclinical research. This article is protected by copyright. All rights reserved.
U2 - 10.1113/JP280908
DO - 10.1113/JP280908
M3 - Journal article
C2 - 33932956
VL - 600
SP - 1135
EP - 1154
JO - The Journal of Physiology
JF - The Journal of Physiology
SN - 0022-3751
IS - 5
ER -
ID: 261110327