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Oleate ameliorates palmitate-induced reduction of NAMPT activity and NAD levels in primary human hepatocytes and hepatocarcinoma cells

Overview of attention for article published in Lipids in Health and Disease, October 2017
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Title
Oleate ameliorates palmitate-induced reduction of NAMPT activity and NAD levels in primary human hepatocytes and hepatocarcinoma cells
Published in
Lipids in Health and Disease, October 2017
DOI 10.1186/s12944-017-0583-6
Pubmed ID
Authors

Melanie Penke, Susanne Schuster, Theresa Gorski, Rolf Gebhardt, Wieland Kiess, Antje Garten

Abstract

Nicotinamide 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. HepG2 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 (14)C-nicotinamide. Lipids were stained by Oil red O staining. Palmitate 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. Palmitate 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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Mendeley readers

Mendeley readers

The data shown below were compiled from readership statistics for 39 Mendeley readers of this research output. Click here to see the associated Mendeley record.

Geographical breakdown

Country Count As %
Unknown 39 100%

Demographic breakdown

Readers by professional status Count As %
Researcher 7 18%
Student > Master 6 15%
Student > Ph. D. Student 4 10%
Student > Doctoral Student 3 8%
Student > Bachelor 3 8%
Other 7 18%
Unknown 9 23%
Readers by discipline Count As %
Biochemistry, Genetics and Molecular Biology 9 23%
Medicine and Dentistry 6 15%
Agricultural and Biological Sciences 5 13%
Pharmacology, Toxicology and Pharmaceutical Science 2 5%
Engineering 2 5%
Other 4 10%
Unknown 11 28%
Attention Score in Context

Attention Score in Context

This research output has an Altmetric Attention Score of 1. This is our high-level measure of the quality and quantity of online attention that it has received. This Attention Score, as well as the ranking and number of research outputs shown below, was calculated when the research output was last mentioned on 02 June 2018.
All research outputs
#17,917,778
of 23,005,189 outputs
Outputs from Lipids in Health and Disease
#927
of 1,457 outputs
Outputs of similar age
#231,064
of 323,064 outputs
Outputs of similar age from Lipids in Health and Disease
#17
of 28 outputs
Altmetric has tracked 23,005,189 research outputs across all sources so far. This one is in the 19th percentile – i.e., 19% of other outputs scored the same or lower than it.
So far Altmetric has tracked 1,457 research outputs from this source. They typically receive more attention than average, with a mean Attention Score of 8.1. This one is in the 32nd percentile – i.e., 32% of its peers scored the same or lower than it.
Older research outputs will score higher simply because they've had more time to accumulate mentions. To account for age we can compare this Altmetric Attention Score to the 323,064 tracked outputs that were published within six weeks on either side of this one in any source. This one is in the 23rd percentile – i.e., 23% of its contemporaries scored the same or lower than it.
We're also able to compare this research output to 28 others from the same source and published within six weeks on either side of this one. This one is in the 35th percentile – i.e., 35% of its contemporaries scored the same or lower than it.