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Nicotinamide riboside affects toll‐like receptor 4‐NF‐κB pathway via sirtuin‐dependent and –independent ways in AML12 hepatocytes
Author(s) -
Lee Hee Jae,
Yang Soo Jin
Publication year - 2016
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.30.1_supplement.lb372
Subject(s) - gene knockdown , sirtuin , sirtuin 1 , viability assay , sirt3 , chemistry , receptor , inflammation , gene silencing , nad+ kinase , biology , cancer research , microbiology and biotechnology , cell , biochemistry , apoptosis , immunology , downregulation and upregulation , gene , enzyme
The objective of this study was to explore the potential role of nicotinamide riboside (NR) on Sirt1/3. The NAD+ precursor NR is a third vitamin B3. Recent studies have suggested that NR shown protective effects for hearing loss, high‐fat induced obesity, and Alzheimer's disease. Mouse hepatocytes were treated with NR (10 μM and 10 mM) for 24 hours. RNA interference (RNAi)‐mediated gene silencing was performed for Sirt1 and Sirt3 knockdown, and then NR was administered. Inflammatory markers and Sirt pathway were analyzed. AML12 cell viability which was reduced by PA was increased by low concentrations of NR treatment. Sirt1 was significantly up‐regulated by NR. The NR treatment led to the up‐regulation of insulin‐sensitizing molecule adiponectin. The levels of CPT‐1 in NR‐treated cells were three times higher than those of CON. Hepatic pro‐inflammatory markers including TNF‐alpha and IL‐6 were decreased in NR‐treated cells. In addition, caspase 1, a component of NOD‐like receptor family, pyrin domain containing 3 inflammasome, was decreased by NR. Sirt1 knockdown triggered hepatic metaflammation. Sirt1 was necessary to show protective effects for inflammation in AML12 NR‐treated cells. Sirt3 knockdown resulted in decreased levels of Sirt1 and Sirt6. NR treatment altered toll‐like receptor 4‐NF‐κB, which was independent of Sirt3. NR decreased level of fatty acid synthase, and these effects were observed in Sirt3 knockdown group. These data demonstrated that NR enhances cell viability, and affects TLR4‐NF‐κB pathway via sirtuin‐dependent and ‐independent ways in hepatocytes.