The Impact of a Ketogenic Diet and Liver Dysfunction on Serum Very Long-Chain Fatty Acids Levels

Lipids ◽  
2013 ◽  
Vol 48 (4) ◽  
pp. 405-409 ◽  
Author(s):  
T. J. Stradomska ◽  
M. Bachański ◽  
J. Pawłowska ◽  
M. Syczewska ◽  
A. Stolarczyk ◽  
...  
2018 ◽  
Vol 314 (6) ◽  
pp. E605-E619 ◽  
Author(s):  
Stewart Jeromson ◽  
Ivor Mackenzie ◽  
Mary K. Doherty ◽  
Phillip D. Whitfield ◽  
Gordon Bell ◽  
...  

In striated muscle, eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) have differential effects on the metabolism of glucose and differential effects on the metabolism of protein. We have shown that, despite similar incorporation, treatment of C2C12 myotubes (CM) with EPA but not DHA improves glucose uptake and protein accretion. We hypothesized that these differential effects of EPA and DHA may be due to divergent shifts in lipidomic profiles leading to altered proteomic profiles. We therefore carried out an assessment of the impact of treating CM with EPA and DHA on lipidomic and proteomic profiles. Fatty acid methyl esters (FAME) analysis revealed that both EPA and DHA led to similar but substantials changes in fatty acid profiles with the exception of arachidonic acid, which was decreased only by DHA, and docosapentanoic acid (DPA), which was increased only by EPA treatment. Global lipidomic analysis showed that EPA and DHA induced large alterations in the cellular lipid profiles and in particular, the phospholipid classes. Subsequent targeted analysis confirmed that the most differentially regulated species were phosphatidylcholines and phosphatidylethanolamines containing long-chain fatty acids with five (EPA treatment) or six (DHA treatment) double bonds. As these are typically membrane-associated lipid species we hypothesized that these treatments differentially altered the membrane-associated proteome. Stable isotope labeling by amino acids in cell culture (SILAC)-based proteomics of the membrane fraction revealed significant divergence in the effects of EPA and DHA on the membrane-associated proteome. We conclude that the EPA-specific increase in polyunsaturated long-chain fatty acids in the phospholipid fraction is associated with an altered membrane-associated proteome and these may be critical events in the metabolic remodeling induced by EPA treatment.


Author(s):  
Ilhame Diboun ◽  
Layla Al-Mansoori ◽  
Hend Al-Jaber ◽  
Omar Albagha ◽  
Mohamed A Elrayess

Abstract Background The global diabetes epidemic is largely attributed to obesity-triggered metabolic syndrome. However, the impact of insulin resistance (IR) prior to obesity on the high prevalence of diabetes and the molecular mediators remain largely unknown. This study aims to compare the metabolic profiling of apparently healthy lean/overweight participants with IR and insulin sensitivity (IS), and identify the metabolic pathways underlying IR. Methods In this cross-sectional study, clinical and metabolic data for 200 seemingly healthy young female participants (100 IR and 100 IS) was collected from Qatar Biobank. Orthogonal partial least square analysis was performed to assess the extent of separation between individuals from the 2 groups based on measured metabolites. Classical linear models were used to identify the metabolic signature of IR, followed by elastic-net-regularized generalized linear model (GLMNET) and receiver operating characteristic (ROC) analysis to determine top metabolites associated with IR. Results Compared to lean/overweight participants with IS, those with IR showed increased androgenic steroids, including androsterone glucuronide, in addition to various microbiota byproducts, such as the phenylalanine derivative carboxyethylphenylalanine. On the other hand, participants with IS had elevated levels of long-chain fatty acids. A ROC analysis suggested better discriminatory performance using 20 metabolites selected by GLMNET in comparison to the classical clinical traits (area under curve: 0.93 vs 0.73, respectively). Conclusion Our data confirm the multifactorial mechanism of IR with a diverse spectrum of emerging potential biomarkers, including steroids, long-chain fatty acids, and microbiota metabolites. Further studies are warranted to validate these markers for diagnostic and therapeutic applications.


1993 ◽  
Vol 122 (5) ◽  
pp. 724-726 ◽  
Author(s):  
Christiane Theda ◽  
Robert C. Woody ◽  
Sakkubai Naidu ◽  
Ann B. Moser ◽  
Hugo W. Moser

2020 ◽  
Vol 21 (2) ◽  
pp. 641 ◽  
Author(s):  
Thomas Nury ◽  
Margaux Doria ◽  
Gérard Lizard ◽  
Anne Vejux

In the case of neurodegenerative pathologies, the therapeutic arsenal available is often directed towards the consequences of the disease. The purpose of this study is, therefore, to evaluate the ability of docosahexaenoic acid (DHA), a molecule present in certain foods and considered to have health benefits, to inhibit the cytotoxic effects of very long-chain fatty acids (C24:0, C26:0), which can contribute to the development of some neurodegenerative diseases. The effect of DHA (50 µM) on very long-chain fatty acid-induced toxicity was studied by several complementary methods: phase contrast microscopy to evaluate cell viability and morphology, the MTT test to monitor the impact on mitochondrial function, propidium iodide staining to study plasma membrane integrity, and DHE staining to measure oxidative stress. A Western blot assay was used to assess autophagy through modification of LC3 protein. The various experiments were carried out on the cellular model of 158N murine oligodendrocytes. In 158N cells, our data establish that DHA is able to inhibit all tested cytotoxic effects induced by very long-chain fatty acids.


2020 ◽  
Vol 4 (Supplement_2) ◽  
pp. 682-682 ◽  
Author(s):  
Kayla Dillard ◽  
Morgan Coffin ◽  
Gabriella Hernandez ◽  
Victoria Smith ◽  
Catherine Johnson ◽  
...  

Abstract Objectives Non-alcoholic fatty liver disease (NAFLD) represents the major cause of pediatric chronic liver pathology in the United States. The objective of this study was to compare the relative effect of inclusion of isocaloric amounts of saturated medium-chain fatty acids (hydrogenated coconut oil), saturated long-chain fatty acids (lard) and unsaturated long-chain fatty acids (olive oil) on endpoints of NAFLD and insulin resistance. Methods Thirty-eight 15-d-old Iberian pigs were fed 1 of 4 diets containing (g/kg body weight × d) 1) control (CON; n = 8): 0 g fructose, 10.5 g fat, and 187 kcal metabolizable energy (ME), 2) lard (LAR; n = 10): 21.6 g fructose, 17.1 g fat (100% lard) and 299 kcal ME, 3) hydrogenated coconut oil (COCO; n = 10): 21.6 g fructose, 16.9 g fat (42.5% lard and 57.5% coconut oil) and 299 kcal ME, and 4) olive oil (OLV, n = 10): 21.6 g fructose, 17.1 g fat (43.5% lard and 56.5% olive oil) and 299 kcal ME, for 9 consecutive weeks. Body weight was recorded every 3 d. Serum markers of liver injury and dyslipidemia were measured on d 60 at 2 h post feeding, with all other serum measures assessed on d 70. Liver tissue was collected on d 70 for histology, triacylglyceride (TG) quantification, and metabolomics analysis. Results Tissue histology indicated the presence of steatosis in LAR, COCO and OLV compared with CON (P ≤ 0.001), with a further increase in in non-alcoholic steatohepatitis (NASH) in OLV and COCO compared with LAR (P ≤ 0.01). Alanine and aspartate aminotransferases were higher in COCO and OLV (P ≤ 0.01) than CON. All treatment groups had lower liver concentrations of methyl donor's choline and betaine versus CON, while bile acids were differentially changed (P ≤ 0.05). COCO had higher levels of TGs with less carbons (Total carbons < 52) than all other groups (P ≤ 0.05). Several long-chain acylcarnitines involved in fat oxidation were higher in OLV versus all other groups (P ≤ 0.05). Conclusions Inclusion of fats enriched in medium-chain saturated and long-chain unsaturated fatty acids in a high-fructose high-fat diet increased liver injury, compared with fats with a long-chain saturated fatty acid profile. Further research is required to investigate the mechanisms causing this difference in physiological response to these dietary fat sources. Funding Sources ARI, AcornSeekers.


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