ArticleLipids in health and disease2017
Oleate ameliorates palmitate-induced reduction of NAMPT activity and NAD levels in primary human hepatocytes and hepatocarcinoma cells.
Article in Lipids in health and disease, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.
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14 citing papers in PubMed, 28 citations in OpenAlex.
- Review
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- Palmitic acid causes hepatocyte inflammation by suppressing the BMAL1-NADJournal of physiology and biochemistry · 2024Article
- Determining the temporal, dose, and composition effects of nutritional substrates in an in vitro model of intrahepatocellular triglyceride accumulation.Physiological reports · 2022Article
- Isolated and combined impact of dietary olive oil and exercise on markers of health and energy metabolism in female mice.The Journal of nutritional biochemistry · 2022Article
- NAD+ depletion enhances reovirus-induced oncolysis in multiple myeloma.Molecular therapy oncolytics · 2022Article
- Scale bar of aging trajectories for screening personal rejuvenation treatments.Computational and structural biotechnology journal · 2022Article
- Critical Role of Astrocyte NADThe Journal of neuroscience : the official journal of the Society for Neuroscience · 2021Article
- The diversity and breadth of cancer cell fatty acid metabolism.Cancer & metabolism · 2021Review
- NAMPT and BMAL1 Are Independently Involved in the Palmitate-Mediated Induction of Neuroinflammation in Hypothalamic Neurons.Frontiers in endocrinology · 2020Article
- Sorafenib-Induced Apoptosis in Hepatocellular Carcinoma Is Reversed by SIRT1.International journal of molecular sciences · 2019Article
- Heterogeneity of fatty acid metabolism in breast cancer cells underlies differential sensitivity to palmitate-induced apoptosis.Molecular oncology · 2018Article
- Salubrinal abrogates palmitate-induced leptin resistance and endoplasmic reticulum stress via nuclear factor kappa-light-chain-enhancer of activated B cell pathway in mHypoE-44 hypothalamic neurons.Diabetes, metabolic syndrome and obesity : targets and therapy · 2018Article
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6 authors at 1 institution in 1 country.
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No grant is acknowledged in the PubMed record.
Abstract
backgroundNicotinamide phosphoribosyltransferase (NAMPT) and nicotinamide adenine dinucleotide (NAD) levels are crucial for liver function. The saturated fatty acid palmitate and the unsaturated fatty acid oleate are the main free fatty acids in adipose tissue and human diet. We asked how these fatty acids affect cell survival, NAMPT and NAD levels in HepG2 cells and primary human hepatocytes.
methodsHepG2 cells were stimulated with palmitate (0.5mM), oleate (1mM) or a combination of both (0.5mM/1mM) as well as nicotinamide mononucleotide (NMN) (0.5 mM) or the specific NAMPT inhibitor FK866 (10nM). Cell survival was measured by WST-1 assay and Annexin V/propidium iodide staining. NAD levels were determined by NAD/NADH Assay or HPLC. Protein and mRNA levels were analysed by Western blot analyses and qPCR, respectively. NAMPT enzyme activity was measured using radiolabelled
resultsPalmitate significantly reduced cell survival and induced apoptosis at physiological doses. NAMPT activity and NAD levels significantly declined after 48h of palmitate. In addition, NAMPT mRNA expression was enhanced which was associated with increased NAMPT release into the supernatant, while intracellular NAMPT protein levels remained stable. Oleate alone did not influence cell viability and NAMPT activity but ameliorated the negative impact of palmitate on cell survival, NAMPT activity and NAD levels, as well as the increased NAMPT mRNA expression and secretion. NMN was able to normalize intracellular NAD levels but did not ameliorate cell viability after co-stimulation with palmitate. FK866, a specific NAMPT inhibitor did not influence lipid accumulation after oleate-treatment.
conclusionsPalmitate targets NAMPT activity with a consequent cellular depletion of NAD. Oleate protects from palmitate-induced apoptosis and variation of NAMPT and NAD levels. Palmitate-induced cell stress leads to an increase of NAMPT mRNA and accumulation in the supernatant. However, the proapoptotic action of palmitate seems not to be mediated by decreased NAD levels.
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