PMID- 33846538
OWN - NLM
STAT- MEDLINE
DCOM- 20210827
LR  - 20240229
IS  - 1530-0307 (Electronic)
IS  - 0023-6837 (Linking)
VI  - 101
IP  - 9
DP  - 2021 Sep
TI  - Nicotinamide riboside, an NAD(+) precursor, attenuates inflammation and oxidative 
      stress by activating sirtuin 1 in alcohol-stimulated macrophages.
PG  - 1225-1237
LID - S0023-6837(22)00583-9 [pii]
LID - 10.1038/s41374-021-00599-1 [doi]
AB  - Macrophages play an essential role in alcohol-induced inflammation and oxidative 
      stress. We investigated the effects of nicotinamide riboside (NR), a natural 
      nicotinamide adenine dinucleotide (NAD(+)) precursor, on alcohol-induced 
      inflammation and oxidative stress in macrophages. NR significantly decreased 
      ethanol-induced inflammatory gene expression, with a concomitant decrease in 
      nuclear translocation of nuclear factor kappaB p65 in RAW 264.7 macrophages and mouse 
      bone marrow-derived macrophages (BMDMs). In macrophages incubated with ethanol or 
      acetaldehyde, NR abolished the accumulation of cellular reactive oxygen species. 
      Ethanol decreased sirtuin 1 (SIRT1) expression and activity, and cellular NAD(+) 
      level while inducing pro-inflammatory gene expression. However, NR markedly 
      attenuated the changes. SIRT1 inhibition augmented ethanol-induced inflammatory 
      gene expression, but its activation elicited opposing effects. Also, ethanol did 
      not alter glycolysis but increased glycolytic capacity, glycolytic reserve, and 
      non-glycolytic acidification, with concomitant increases in hypoxia-induced 
      factor 1alpha expression and activity, phosphorylation of pyruvate dehydrogenase, and 
      extracellular lactate levels. Interestingly, ethanol increased mitochondrial 
      respiration and ATP production but decreased maximal respiration and spare 
      respiration capacity. The latter was linked to decreases in mitochondrial copy 
      numbers. NR abolished the ethanol-induced metabolic changes in the glycolytic and 
      oxidative phosphorylation pathways in RAW 264.7 macrophages. In conclusion, NR 
      exerts anti-inflammatory and antioxidant properties by abrogating the inhibitory 
      effects of ethanol on the SIRT1 pathway by increasing Sirt1 expression and its 
      activator, NAD(+). Also, SIRT1 activation and normalization of ethanol-induced 
      changes in NAD(+)/NADH ratios by NR are likely crucial to counteract the changes 
      in energy phenotypes of macrophages exposed to ethanol.
CI  - (c) 2021. The Author(s), under exclusive licence to United States and Canadian 
      Academy of Pathology.
FAU - Kang, Hyunju
AU  - Kang H
AD  - Department of Nutritional Sciences, University of Connecticut, Storrs, CT, USA.
FAU - Park, Young-Ki
AU  - Park YK
AD  - Department of Nutritional Sciences, University of Connecticut, Storrs, CT, USA.
FAU - Lee, Ji-Young
AU  - Lee JY
AD  - Department of Nutritional Sciences, University of Connecticut, Storrs, CT, USA. 
      ji-young.lee@uconn.edu.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20210412
PL  - United States
TA  - Lab Invest
JT  - Laboratory investigation; a journal of technical methods and pathology
JID - 0376617
RN  - 0 (Anti-Inflammatory Agents)
RN  - 0 (Antioxidants)
RN  - 0 (Pyridinium Compounds)
RN  - 0I8H2M0L7N (nicotinamide-beta-riboside)
RN  - 25X51I8RD4 (Niacinamide)
RN  - 3K9958V90M (Ethanol)
RN  - EC 3.5.1.- (Sirt1 protein, mouse)
RN  - EC 3.5.1.- (Sirtuin 1)
SB  - IM
MH  - Animals
MH  - Anti-Inflammatory Agents/pharmacology
MH  - Antioxidants/pharmacology
MH  - Ethanol/adverse effects
MH  - Inflammation/*metabolism
MH  - *Macrophages/drug effects/metabolism
MH  - Mice
MH  - Niacinamide/*analogs & derivatives/pharmacology
MH  - Oxidative Stress/*drug effects
MH  - Pyridinium Compounds/*pharmacology
MH  - RAW 264.7 Cells
MH  - Sirtuin 1/*metabolism
EDAT- 2021/04/14 06:00
MHDA- 2021/08/28 06:00
CRDT- 2021/04/13 06:22
PHST- 2020/12/20 00:00 [received]
PHST- 2021/03/08 00:00 [accepted]
PHST- 2021/03/06 00:00 [revised]
PHST- 2021/04/14 06:00 [pubmed]
PHST- 2021/08/28 06:00 [medline]
PHST- 2021/04/13 06:22 [entrez]
AID - S0023-6837(22)00583-9 [pii]
AID - 10.1038/s41374-021-00599-1 [doi]
PST - ppublish
SO  - Lab Invest. 2021 Sep;101(9):1225-1237. doi: 10.1038/s41374-021-00599-1. Epub 2021 
      Apr 12.