Nicotinamide riboside regulates inflammation and mitochondrial markers in AML12 hepatocytes
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BACKGROUND/OBJECTIVES: The NAD+ precursor nicotinamide riboside (NR) is a type of vitamin B3 found in cow’s milk and yeast-containing food products such as beer. Recent studies suggested that NR prevents hearing loss, high-fat diet-induced obesity, Alzheimer's disease, and mitochondrial myopathy. The objective of this study was to investigate the effects of NR on inflammation and mitochondrial biogenesis in AML12 mouse hepatocytes. MATERIALS/METHODS: A subset of hepatocytes was treated with palmitic acid (PA; 250 μM) for 48 h to induce hepatocyte steatosis. The hepatocytes were treated with NR (10 μM and 10 mM) for 24 h with and without PA. The cell viability and the levels of sirtuins, inflammatory markers, and mitochondrial markers were analyzed. RESULTS: Cytotoxicity of NR was examined by PrestoBlue assay. Exposure to NR had no effect on cell viability or morphology. Gene expression of sirtuin 1 (Sirt1) and Sirt3 was significantly upregulated by NR in PA-treated hepatocytes. However, Sirt1 activities were increased in hepatocytes treated with low-dose NR. Hepatic pro-inflammatory markers including tumor necrosis factor-alpha and interleukin-6 were decreased in NR-treated cells. NR upregulated anti-inflammatory molecule adiponectin, and, tended to down-regulate hepatokine fetuin-A in PA-treated hepatocytes, suggesting its inverse regulation on these cytokines. NR increased levels of mitochondrial markers including peroxisome proliferator-activated receptor γ coactivator-1α, carnitine palmitoyltransferase 1, uncoupling protein 2, transcription factor A, mitochondrial and mitochondrial DNA in PA-treated hepatocytes. CONCLUSIONS: These data demonstrated that NR attenuated hepatic inflammation and increased levels of mitochondrial markers in hepatocytes.
Abstract
BACKGROUND/OBJECTIVES: The NAD+ precursor nicotinamide riboside (NR) is a type of vitamin B3 found in cow’s milk and yeast-containing food products such as beer. Recent studies suggested that NR prevents hearing loss, high-fat diet-induced obesity, Alzheimer's disease, and mitochondrial myopathy. The objective of this study was to investigate the effects of NR on inflammation and mitochondrial biogenesis in AML12 mouse hepatocytes. MATERIALS/METHODS: A subset of hepatocytes was treated with palmitic acid (PA; 250 μM) for 48 h to induce hepatocyte steatosis. The hepatocytes were treated with NR (10 μM and 10 mM) for 24 h with and without PA. The cell viability and the levels of sirtuins, inflammatory markers, and mitochondrial markers were analyzed. RESULTS: Cytotoxicity of NR was examined by PrestoBlue assay. Exposure to NR had no effect on cell viability or morphology. Gene expression of sirtuin 1 (Sirt1) and Sirt3 was significantly upregulated by NR in PA-treated hepatocytes. However, Sirt1 activities were increased in hepatocytes treated with low-dose NR. Hepatic pro-inflammatory markers including tumor necrosis factor-alpha and interleukin-6 were decreased in NR-treated cells. NR upregulated anti-inflammatory molecule adiponectin, and, tended to down-regulate hepatokine fetuin-A in PA-treated hepatocytes, suggesting its inverse regulation on these cytokines. NR increased levels of mitochondrial markers including peroxisome proliferator-activated receptor γ coactivator-1α, carnitine palmitoyltransferase 1, uncoupling protein 2, transcription factor A, mitochondrial and mitochondrial DNA in PA-treated hepatocytes. CONCLUSIONS: These data demonstrated that NR attenuated hepatic inflammation and increased levels of mitochondrial markers in hepatocytes.
참고문헌 (55)
- Trammell SA, "Nicotinamide riboside is a major NAD+ precursor vitamin in cow milk", J Nutr, 146, pp.957~963 (2016)
- Belenky P, "Nicotinamide riboside promotes Sir2 silencing and extends lifespan via Nrk and Urh1", Pnp1, Cell, pp.2007, 129[DOI]
- Bieganowski P, "Discoveries of nicotinamide riboside as a nutrient and conserved NRK genes establish a Preiss-Handler independent route to NAD+ in fungi and humans", Cell, 117, pp.495~502 (2004)
- Julius U, "Niacin as antidyslipidemic drug", Can J Physiol Pharmacol, 93, pp.1043~1054 (2015)
- Bogan KL, "Nicotinic acid, nicotinamide, and nicotinamide riboside: a molecular evaluation of NAD+ precursor vitamins in human nutrition", Annu Rev Nutr, 28, pp.115~130 (2008)
- Yang SJ, "Nicotinamide improves glucose metabolism and affects the hepatic NAD-sirtuin pathway in a rodent model of obesity and type 2 diabetes", J Nutr Biochem, 25, pp.66~72 (2014)
- Shima K, "A role of nicotinamide-induced increase in pancreatic β-cell mass on blood glucose control after discontinuation of the treatment in partially pancreatectomized OLETF rats", Diabetes Res Clin Pract, 41, pp.1~8 (1998)
- Knip M, "Safety of high-dose nicotinamide: a review", Diabetologia, 43, pp.1337~1345 (2000)
- Trammell SA, "Nicotinamide riboside is uniquely and orally bioavailable in mice and humans", Nat Commun, 7, pp.12948~ (2016)
- Cantó C, "The NAD+ precursor nicotinamide riboside enhances oxidative metabolism and protects against high-fat diet-induced obesity", Cell Metab, 15, pp.838~847 (2012)
- Brown KD, "Activation of SIRT3 by the NAD⁺ precursor nicotinamide riboside protects from noise-induced hearing loss", Cell Metab, 20, pp.1059~1068 (2014)
- Khan NA, "Effective treatment of mitochondrial myopathy by nicotinamide riboside, a vitamin B3", EMBO Mol Med, 6, pp.721~731 (2014)
- Trammell SA, "Nicotinamide riboside opposes type 2 diabetes and neuropathy in mice", Sci Rep, 6, pp.26933~ (2016)
- Gariani K, "Eliciting the mitochondrial unfolded protein response by nicotinamide adenine dinucleotide repletion reverses fatty liver disease in mice", Hepatology, 63, pp.1190~1204 (2016)
- 이희재, "Nicotinamide Riboside Ameliorates Hepatic Metaflammation by Modulating NLRP3 Inflammasome in a Rodent Model of Type 2 Diabetes", Journal of Medicinal Food, 18(11), pp.1207~1213 (2015), 한국식품영양과학회[DOI]
- Mukherjee S, "Nicotinamide adenine dinucleotide biosynthesis promotes liver regeneration", Hepatology, 65, pp.616~630 (2017)
- Zhou CC, "Hepatic NAD+ deficiency as a therapeutic target for non-alcoholic fatty liver disease in ageing", Br J Pharmacol, 173, pp.2352~2368 (2016)
- Stafeev IS, "Molecular mechanisms of latent inflammation in metabolic syndrome. possible role of sirtuins and peroxisome proliferatoractivated receptor type γ", Biochemistry (Mosc), 80, pp.1217~1226 (2015)
- Mendes KL, "Nuclear sirtuins and inflammatory signaling pathways", Cytokine Growth Factor Rev, 38, pp.98~105 (2017)
- Ding RB, "Emerging roles of SIRT1 in fatty liver diseases", Int J Biol Sci, 13, pp.852~867 (2017)
- Liu P, "Sirtuin 3-induced macrophage autophagy in regulating NLRP3 inflammasome activation", Biochim Biophys Acta Mol Basis Dis, 1864, pp.764~777 (2018)
- Paulin R, "Sirtuin 3 deficiency is associated with inhibited mitochondrial function and pulmonary arterial hypertension in rodents and humans", Cell Metab, 20, pp.827~839 (2014)
- Gleave JA, "Sirtuin 3 rescues neurons through the stabilisation of mitochondrial biogenetics in the virally-expressing mutant α-synuclein rat model of parkinsonism", Neurobiol Dis, 106, pp.133~146 (2017)
- Li Y, "Activation of sirtuin 3 by silybin attenuates mitochondrial dysfunction in cisplatin-induced acute kidney injury", Front Pharmacol, 8, pp.178~ (2017)
- Nemoto S, "Nutrient availability regulates SIRT1 through a forkhead-dependent pathway", Science, 306, pp.2105~2108 (2004)
- Noriega LG, "CREB and ChREBP oppositely regulate SIRT1 expression in response to energy availability", EMBO Rep, 12, pp.1069~1076 (2011)
- Hayashida S, "Fasting promotes the expression of SIRT1, an NAD+- dependent protein deacetylase, via activation of PPARα in mice", Mol Cell Biochem, 339, pp.285~292 (2010)
- Okazaki M, "PPARβ", δ regulates the human SIRT1 gene transcription via Sp1, 2010, pp.57, 403~413
- Han L, "SIRT1 is regulated by a PPARγ-SIRT1 negative feedback loop associated with senescence", Nucleic Acids Res, 38, pp.7458~7471 (2010)
- Sasaki T, "Phosphorylation regulates SIRT1 function", PLoS One, 3, pp.e4020~ (2008)
- Nasrin N, "JNK1 phosphorylates SIRT1 and promotes its enzymatic activity", PLoS One, 4, pp.e8414~ (2009)
- Guo X, "DYRK1A and DYRK3 promote cell survival through phosphorylation and activation of SIRT1", J Biol Chem, 285, pp.13223~13232 (2010)
- Yang Y, "SIRT1 sumoylation regulates its deacetylase activity and cellular response to genotoxic stress", Nat Cell Biol, 9, pp.1253~1262 (2007)
- Kim EJ, "Active regulator of SIRT1 cooperates with SIRT1 and facilitates suppression of p53 activity", Mol Cell, 28, pp.277~290 (2007)
- Picard F, "Sirt1 promotes fat mobilization in white adipocytes by repressing PPAR-γ", Nature, 429, pp.771~776 (2004)
- Kim JE, "DBC1 is a negative regulator of SIRT1", Nature, 451, pp.583~586 (2008)
- Zhao W, "Negative regulation of the deacetylase SIRT1 by DBC1", Nature, 451, pp.587~590 (2008)
- Houtkooper RH, "Sirtuins as regulators of metabolism and healthspan", Nat Rev Mol Cell Biol, 13, pp.225~238 (2012)
- Cohen JC, "Human fatty liver disease: old questions and new insights", Science, 332, pp.1519~1523 (2011)
- Kinoshita T, "NLRP3 mediates NF-κ B activation and cytokine induction in microbially induced and sterile inflammation", PLoS One, 10, pp.e0119179~ (2015)
- Tak PP, "NF-κB: a key role in inflammatory diseases", J Clin Invest, 107, pp.7~11 (2001)
- Lin X, "Differential expression of insulin receptor tyrosine kinase inhibitor (fetuin) gene in a model of diet-induced obesity", Life Sci, 63, pp.145~153 (1998)
- Lee HJ, "Involvement of resveratrol in crosstalk between adipokine adiponectin and hepatokine fetuin-A in vivo and in vitro", J Nutr Biochem, 26, pp.1254~1260 (2015)
- Begriche K, "Mitochondrial dysfunction in NASH: causes, consequences and possible means to prevent it", Mitochondrion, 6, pp.1~28 (2006)
- Sheng B, "Impaired mitochondrial biogenesis contributes to mitochondrial dysfunction in Alzheimer's disease", J Neurochem, 120, pp.419~429 (2012)
- Ren J, "Mitochondrial biogenesis in the metabolic syndrome and cardiovascular disease", J Mol Med (Berl), 88, pp.993~1001 (2010)
- López-Lluch G, "Mitochondrial biogenesis and healthy aging", Exp Gerontol, 43, pp.813~819 (2008)
- Austin S, "PGC1α and mitochondrial metabolism--emerging concepts and relevance in ageing and neurodegenerative disorders", J Cell Sci, 125, pp.4963~4971 (2012)
- Goffart S, "Regulation and co-ordination of nuclear gene expression during mitochondrial biogenesis", Exp Physiol, 88, pp.33~40 (2003)
- Handschin C, "Peroxisome proliferator-activated receptor gamma coactivator 1 coactivators, energy homeostasis, and metabolism", Endocr Rev, 27, pp.728~735 (2006)
- Gong B, "Nicotinamide riboside restores cognition through an upregulation of proliferator-activated receptor-γ coactivator 1α regulated β-secretase 1 degradation and mitochondrial gene expression in Alzheimer's mouse models", Neurobiol Aging, 34, pp.1581~1588 (2013)
- Fernandez-Marcos PJ, "Regulation of PGC-1α, a nodal regulator of mitochondrial biogenesis", Am J Clin Nutr, 93, pp.884S~890S (2011)
- Aharoni-Simon M, "Fatty liver is associated with impaired activity of PPARγ-coactivator 1α (PGC1α) and mitochondrial biogenesis in mice", Lab Invest, 91, pp.1018~1028 (2011)
- Finck BN, "PGC-1 coactivators: inducible regulators of energy metabolism in health and disease", J Clin Invest, 116, pp.615~622 (2006)
- Puigserver P, "Tissue-specific regulation of metabolic pathways through the transcriptional coactivator PGC1-α", Int J Obes (Lond), 29(Suppl 1), pp.S5~S9 (2005)