ArticleBiochimica et biophysica acta2015
Nicotinamide ameliorates palmitate-induced ER stress in hepatocytes via cAMP/PKA/CREB pathway-dependent Sirt1 upregulation.
Article in Biochimica et biophysica acta, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers.
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Who cites it
27 citing papers in PubMed, 50 citations in OpenAlex.
- Nicotinamide mononucleotide attenuates hepatic endoplasmic reticulum stress and modulates circadian rhythms in young mice with diet-induced obesity.Nutrition research and practice · 2026Article
- Niacin Derivatives in MASLD: Metabolic and Therapeutic Insights.Nutrients · 2026Review
- NAD + in fatty liver disease: mechanistic insights and associated targets.Cell biology and toxicology · 2025Review
- The role of the tryptophan-NAD + pathway in a mouse model of severe malnutrition induced liver dysfunction.Nature communications · 2022Article
- The Role of Sirtuin 1 in Palmitic Acid-Induced Endoplasmic Reticulum Stress in Cardiac Myoblasts.Life (Basel, Switzerland) · 2022Article
- Nicotinamide supplementation in diabetic nonalcoholic fatty liver disease patients: randomized controlled trial.Therapeutic advances in chronic disease · 2022Article
- ER stress-related mRNA-lncRNA co-expression gene signature predicts the prognosis and immune implications of esophageal cancer.American journal of translational research · 2022Article
- Oxidative stress and inflammation regulation of sirtuins: New insights into common oral diseases.Frontiers in physiology · 2022Review
- Roflupram protects against rotenone-induced neurotoxicity and facilitates α-synuclein degradation in Parkinson's disease models.Acta pharmacologica Sinica · 2021Article
- Critical Role of Astrocyte NADThe Journal of neuroscience : the official journal of the Society for Neuroscience · 2021Article
- Nicotinamide N-methyltransferase upregulation via the mTORC1-ATF4 pathway activation contributes to palmitate-induced lipotoxicity in hepatocytes.American journal of physiology. Cell physiology · 2021Article
- Mechanisms and inhibitors of nicotinamideRSC medicinal chemistry · 2021Review
- Article
- Fuzzy modeling and global optimization to predict novel therapeutic targets in cancer cells.Bioinformatics (Oxford, England) · 2020Article
- Activation of the AMPK-SIRT1 pathway contributes to protective effects of Salvianolic acid A against lipotoxicity in hepatocytes and NAFLD in mice.Frontiers in pharmacology · 2020Article
- Liver X Receptor α-Induced Cannabinoid Receptor 2 Inhibits Ubiquitin-Specific Peptidase 4 Through miR-27b, Protecting Hepatocytes From TGF-β.Hepatology communications · 2019Article
- Procyanidins and Alzheimer's Disease.Molecular neurobiology · 2019Review
- Vitamin B combination reduces fluconazole toxicity in Wistar rats.Daru : journal of Faculty of Pharmacy, Tehran University of Medical Sciences · 2019Article
- Silencing MicroRNA-134 Alleviates Hippocampal Damage and Occurrence of Spontaneous Seizures After Intraventricular Kainic Acid-Induced Status Epilepticus in Rats.Frontiers in cellular neuroscience · 2019Article
- PKA regulates HMGB1 through activation of IGFBP-3 and SIRT1 in human retinal endothelial cells cultured in high glucose.Inflammation research : official journal of the European Histamine Research Society ... [et al.] · 2018Article
Corrections and comments
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Authors and funding
6 authors at 3 institutions in 2 countries.
Funding
Abstract
Nicotinamide (NAM) is the amide of nicotinic acid and a predominant precursor for NAD(+) biosynthesis via the salvage pathway. Sirt1 is a NAD(+)-dependent deacetylase, playing an important role in regulating cellular functions. Although hepatoprotective effect of NAM has been reported, the underlying mechanism remains elusive. ER stress, induced by saturated fatty acids, in specific palmitate, plays a pathological role in the development of nonalcoholic fatty liver disease. This study aims to determine the effect of NAM on palmitate-induced ER stress in hepatocytes and to elucidate molecular mechanisms behind. Both HepG2 cells and primary mouse hepatocytes were exposed to palmitate (conjugated to BSA at a 2:1 M ratio), NAM, or their combination for different durations. Cellular NAD(+) level, Sirt1 expression/activity, ER stress, as well as cAMP/PKA/CREB pathway activation were determined. NAM increased Sirt1 expression and enzymatic activity, which contributes to the ameliorative effect of NAM on palmitate-triggered ER stress. NAM increased intracellular NAD(+) level in hepatocytes, however, blocking the salvage pathway, a pathway for NAD(+) synthesis from NAM, only partially prevented NAM-induced Sirt1 upregulation while completely prevented NAD+ increase in response to NAM. Further mechanistic investigations revealed that NAM elevated intracellular cAMP level via suppressing PDE activity, leading to downstream PKA and CREB activation. Importantly, cAMP/PKA/CREB pathway blockade abolished not only NAM-induced Sirt1 upregulation, but also its protective effect against ER stress. Our results demonstrate that NAM protects hepatocytes against palmitate-induced ER stress in hepatocytes via upregulating Sirt1. Activation of the cAMP/PKA/CREB pathway plays a key role in NAM-induced Sirt1 upregulation.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.