scholarly journals Stable Isotopic Tracer Phospholipidomics Reveals Contributions of Key Phospholipid Biosynthetic Pathways to Low Hepatocyte Phosphatidylcholine to Phosphatidylethanolamine Ratio Induced by Free Fatty Acids

Metabolites ◽  
2021 ◽  
Vol 11 (3) ◽  
pp. 188
Author(s):  
Kang-Yu Peng ◽  
Christopher K Barlow ◽  
Helene Kammoun ◽  
Natalie A Mellett ◽  
Jacquelyn M Weir ◽  
...  
Keyword(s):  
Fatty Acid ◽  
Free Fatty Acid ◽  
Strong Association ◽  
Phospholipid Composition ◽  
Rat Hepatocytes ◽  
Methyl Transferase ◽  
Alcoholic Fatty Liver ◽  
Isotopic Tracer ◽  
Stable Isotopic ◽  
Cytidine Diphosphate

There is a strong association between hepatocyte phospholipid homeostasis and non-alcoholic fatty liver disease (NAFLD). The phosphatidylcholine to phosphatidylethanolamine ratio (PC/PE) often draws special attention as genetic and dietary disruptions to this ratio can provoke steatohepatitis and other signs of NAFLD. Here we demonstrated that excessive free fatty acid (1:2 mixture of palmitic and oleic acid) alone was able to significantly lower the phosphatidylcholine to phosphatidylethanolamine ratio, along with substantial alterations to phospholipid composition in rat hepatocytes. This involved both a decrease in hepatocyte phosphatidylcholine (less prominent) and an increase in phosphatidylethanolamine, with the latter contributing more to the lowered ratio. Stable isotopic tracer phospholipidomic analysis revealed several previously unidentified changes that were triggered by excessive free fatty acid. Importantly, the enhanced cytidine diphosphate (CDP)-ethanolamine pathway activity appeared to be driven by the increased supply of preferred fatty acid substrates. By contrast, the phosphatidylethanolamine N-methyl transferase (PEMT) pathway was restricted by low endogenous methionine and consequently low S-adenosylmethionine, which resulted in a concomitant decrease in phosphatidylcholine and accumulation of phosphatidylethanolamine. Overall, our study identified several previously unreported links in the relationship between hepatocyte free fatty acid overload, phospholipid homeostasis, and the development of NAFLD.

scholarly journals Polyphenol-Rich Extracts from Toona sinensis Bark and Fruit Ameliorate Free Fatty Acid-Induced Lipogenesis through AMPK and LC3 Pathways

2019 ◽  
Vol 8 (10) ◽  
pp. 1664 ◽  
Author(s):  
Yung-Chia Chen ◽  
Hsin-Ju Chen ◽  
Bu-Miin Huang ◽  
Yu-Chi Chen ◽  
Chi-Fen Chang
Keyword(s):  
Fatty Acid ◽  
Liver Disease ◽  
Free Fatty Acid ◽  
Protein Expression ◽  
Lipid Accumulation ◽  
Fatty Acid Synthase ◽  
Regulatory Element ◽  
Autophagic Flux ◽  
Alcoholic Fatty Liver ◽  
Toona Sinensis

Non-alcoholic fatty liver disease (NAFLD) is a chronic liver disease found worldwide. The present study aimed to evaluate the mechanisms of inhibiting lipid accumulation in free fatty acid (FFA)-treated HepG2 cells caused by bark and fruit extracts of Toona sinensis (TSB and TSF). FFA induced lipid and triglyceride (TG) accumulation, which was attenuated by TSB and TSF. TSB and/or TSF promoted phosphorylation of AMP-activated protein kinase (AMPK) and acetyl-coA carboxylase and peroxisome proliferator-activated receptor alpha upregulation. Furthermore, TSB and TSF suppressed FFA-induced liver X receptor, sterol regulatory element-binding transcription protein 1, fatty acid synthase, and stearoyl-CoA desaturase 1 protein expression. Moreover, TSB and/or TSF induced phosphorylation of Unc-51 like autophagy-activating kinase and microtubule-associated protein 1A/1B-light chain 3 expressions. Therefore, TSB and TSF relieve lipid accumulation by attenuating lipogenic protein expression, activating the AMPK pathway, and upregulating the autophagic flux to enhance lipid metabolism. Moreover, TSB and TSF reduced TG contents, implying the therapeutic use of TSB and TSF in NAFLD.

Free fatty-acid uptake by isolated rat hepatocytes

1985 ◽  
Vol 93 (4) ◽  
pp. 313-319 ◽  
Author(s):  
G. Renaud ◽  
M. E. Bouma ◽  
A. Foliot ◽  
R. Infante
Keyword(s):  
Fatty Acid ◽  
Free Fatty Acid ◽  
Rat Hepatocytes ◽  
Fatty Acid Uptake ◽  
Acid Uptake ◽  
Isolated Rat Hepatocytes ◽  
Isolated Rat

scholarly journals Mathematical Modeling of Free Fatty Acid-Induced Non-Alcoholic Fatty Liver Disease (NAFLD)

2020 ◽  
Author(s):  
Hermann-Georg Holzhütter ◽  
Nikolaus Berndt
Keyword(s):  
Fatty Acid ◽  
Liver Disease ◽  
Free Fatty Acid ◽  
Fatty Liver ◽  
Fatty Liver Disease ◽  
Cell Damage ◽  
Generic Model ◽  
Large Individual ◽  
Alcoholic Fatty Liver ◽  
Alcoholic Fatty Liver Disease

SummaryNon-Alcoholic Fatty Liver Disease (NAFLD) is the most common type of chronic liver disease in developed nations. Here we present a generic model of free fatty acid (FFA)-induced NAFLD that constitutes the liver as ensemble of small liver units (LUs) differing in their vulnerability to toxic FFAs and capacities to metabolize FFAs and repair FFA-induced cell damage. The model describes NAFLD as cascading liver failure where failure of few LUs increases the risk for other LUs to fail as well. Model simulations provided the following insights: (1) The large individual differences in the final outcome of NAFLD are already predetermined by the random intra-hepatic heterogeneity of functional capacities; (2) NAFLD amplifies the deleterious impact of secondary damaging although such hits are not necessary for continuous disease worsening; (3) Coexistence of non-steatotic and highly steatotic regions is indicative for the later occurrence of severe NAFLD stages.

scholarly journals A microfluidic patterned model of non-alcoholic fatty liver disease: applications to disease progression and zonation

Lab on a Chip ◽  
2019 ◽  
Vol 19 (18) ◽  
pp. 3022-3031 ◽  
Author(s):  
Beyza Bulutoglu ◽  
Camilo Rey-Bedón ◽  
Young Bok (Abraham) Kang ◽  
Safak Mert ◽  
Martin L. Yarmush ◽  
...  
Keyword(s):  
Fatty Acid ◽  
Liver Disease ◽  
Free Fatty Acid ◽  
Fatty Liver ◽  
Lipid Accumulation ◽  
Fatty Liver Disease ◽  
Wide Spectrum ◽  
Progressive Increase ◽  
Alcoholic Fatty Liver ◽  
Alcoholic Fatty Liver Disease

Non-alcoholic fatty liver disease (NAFLD) involves a progressive increase of lipid accumulation. We created a microfluidic progressive NAFLD platform using free fatty acid gradients to capture the wide spectrum of disease conditions in a single continuous liver tissue.

The effect of ageing on the metabolism of the infective larvae of Strongyloides ratti Sandground, 1925

Parasitology ◽  
1969 ◽  
Vol 59 (1) ◽  
pp. 3-17 ◽  
Author(s):  
J. Barrett
Keyword(s):  
Fatty Acids ◽  
Fatty Acid ◽  
Free Fatty Acid ◽  
Lipid Fraction ◽  
Phospholipid Composition ◽  
Dry Weight ◽  
The Body ◽  
Free Sugars ◽  
Infective Larvae ◽  
Lateral Lines

The infective larvae of S. ratti had a high Qo2 (9·8 μl/mg dry weight/h at 20 °C). Their R.Q. was 0·74 indicating that lipid was the main metabolite.As the infective larvae aged there was an exponential decrease in their infectivity and a corresponding decrease with age in the Qo2 rate of activity and rate of substrate utilization. The R.Q. of fresh and aged larvae was the same showing that there was no change in the substrate being utilized.The infective larvae of S. ratti contained 25% lipid 3% glycogen and 0·25% free sugars (dry weight). The free sugars consisted of glucose and trehalose in approximately equal amounts. Both lipid and glycogen decreased as the larvae aged.Analyses showed all the normal lipid components to be present, the major lipid fraction detected was free fatty acid. As the larvae aged there was a big decrease in the amounts of triglyceride and free fatty acid. There was, however, no difference in the amounts of cholesterol or in the phospholipid composition of fresh and aged larvae.The fatty-acid composition of the larvae was analysed; 68% of the total fatty acids were unsaturated and the major fatty acid was C18:1. As the larvae aged, the fatty acids were not all catabolized at the same rate; the acid C18:1 was the most heavily catabolized decreasing by 75% in 8 days, whilst C20:1 decreased by only half this amount in the same time.The distribution of lipid and glycogen was investigated histochemically. Lipid droplets were confined to the posterior two-thirds of the infective larvae and occurred in the lateral lines, non-contractile parts of the muscles and in the cells of the intestine. As the larvae aged the lipid in the body wall and lateral lines disappeared first. Dark granules, possibly excretory products, accumulated in old larvae. Glycogen was found in the lateral lines throughout the length of the larva.I should like to thank Dr P. Tate for his constant advice and encouragement. This work was carried out during the tenure of a Medical Research Council scholarship.

scholarly journals An Experimental Model of Hepatic Steatosis to Detect Lipid Accumulation

2018 ◽  
pp. 1-10
Author(s):  
Maryam Ammani Lawal ◽  
Gregory Elayeche Oko ◽  
Emmanuel Paul Okoi ◽  
Khuyen Thi Kim Vo ◽  
Shuaib Samirah Isah
Keyword(s):  
Insulin Resistance ◽  
Fatty Acid ◽  
Free Fatty Acid ◽  
Hepatic Steatosis ◽  
Experimental Model ◽  
Hepg2 Cells ◽  
Colorimetric Detection ◽  
Acid Media ◽  
Alcoholic Fatty Liver ◽  
Increased Risk

Obesity is associated with an increased risk of metabolic syndromes such as type 2 diabetes, insulin resistance, dyslipidaemia and non-alcoholic fatty liver disease. Obesity occurs as a result of an imbalance between food intake and energy expenditure leading to excessive accumulation of adipose tissue. NAFLD is the most common liver condition and related to the resistance of insulin. Insulin resistance is associated with an increased influx of lipid into the liver promoting accumulation of hepatic triglyceride. This study aims to develop an experimental model of hepatic steatosis with lipid over-accumulation. HepG2 cells were cultured for 24 hours in free fatty acid media (1:2 palmitic acid and oleic acid respectively). Intracellular lipid content and lipotoxicity were determined by oil red O staining followed by colorimetric detection. This experiment was accomplished by defining the experimental conditions of lipid exposure that leads to significant intracellular fat accumulation in the absence of lipotoxicity with 1 mM of free fatty acid media. As a result, oleic and palmitic acids could be over-accumulated in HepG2 cells. 1 mM free fatty acid media did not affect the cell integrity and did not cause lipotoxicity of the cells.

scholarly journals Free Fatty Acid Receptors as Mediators and Therapeutic Targets in Liver Disease

2021 ◽  
Vol 12 ◽  
Author(s):  
Jordan D. Secor ◽  
Scott C. Fligor ◽  
Savas T. Tsikis ◽  
Lumeng J. Yu ◽  
Mark Puder
Keyword(s):  
Fatty Acids ◽  
Fatty Acid ◽  
Liver Disease ◽  
Free Fatty Acid ◽  
Intestinal Failure ◽  
Alcoholic Fatty Liver ◽  
Liver Health ◽  
Health And Disease ◽  
Free Fatty Acid Receptors ◽  
G Protein Coupled

Free fatty acid receptors (FFARs) are a class of G protein-coupled receptors (GPCRs) that have wide-ranging effects on human physiology. The four well-characterized FFARs are FFAR1/GPR40, FFAR2/GPR43, FFAR3/GPR41, and FFAR4/GPR120. Short-chain (<6 carbon) fatty acids target FFAR2/GPR43 and FFAR3/GPR41. Medium- and long-chain fatty acids (6–12 and 13–21 carbon, respectively) target both FFAR1/GPR40 and FFAR4/GPR120. Signaling through FFARs has been implicated in non-alcoholic fatty liver disease (NAFLD), non-alcoholic steatohepatitis (NASH), intestinal failure-associated liver disease (IFALD), and a variety of other liver disorders. FFARs are now regarded as targets for therapeutic intervention for liver disease, diabetes, obesity, hyperlipidemia, and metabolic syndrome. In this review, we provide an in-depth, focused summary of the role FFARs play in liver health and disease.

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