Fish oil and 3-thia fatty acid have additive effects on lipid metabolism but antagonistic effects on oxidative damage when fed to rats for 50 weeks

Vigerust, Natalya Filipchuk; Cacabelos, Daniel; Burri, Lena; Berge, Kjetil; Wergedahl, Hege; Christensen, Bjørn Jostein; Portero‐Otín, Manuel; Viste, Asgaut; Pamplona, Reinald; Berge, Rolf K.; Bjørndal, Bodil

doi:10.1016/j.jnutbio.2011.08.006

Cited by 31 publications

(38 citation statements)

References 51 publications

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“…These findings suggest that TTA induces both mitochondrial and peroxisomal β-oxidation in heart, supported by two previous studies demonstrating increased myocardial FA oxidation by TTA treatment, associated with reduced cardiac efficiency [22,27]. It has also been shown that TTA induces both CPT-II and ACOX in liver, and to an even larger extent compared to what we report in heart [28]. TTA treatment also resulted in increased activities of cardiac GPAT and FAS.…”

Section: Discussionsupporting

confidence: 90%

Long-term treatment with the pan-PPAR agonist tetradecylthioacetic acid or fish oil is associated with increased cardiac content of n-3 fatty acids in rat

et al. 2012

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BackgroundExcess peroxisome proliferator-activated receptor (PPAR) stimulation has been associated with detrimental health effects including impaired myocardial function. Recently, supplementation with n-3 polyunsaturated fatty acids (PUFA) has been associated with improved left ventricular function and functional capacity in patients with dilated cardiomyopathy. We investigated the long-term effects of the pan-PPAR agonist tetradecylthioacetic acid (TTA) and/or high-dose fish oil (FO) on cardiac fatty acid (FA) composition and lipid metabolism. Male Wistar rats were given one out of four different 25% (w/v) fat diets: control diet; TTA diet; FO diet; or diet containing both TTA and FO.ResultsAfter 50 weeks n-3 PUFA levels were increased by TTA and FO in the heart, whereas liver levels were reduced following TTA administration. TTA was associated with a decrease in arachidonic acid, increased activities of carnitine palmitoyltransferase II, fatty acyl-CoA oxidase, glycerol-3-phosphate acyltransferase, and fatty acid synthase in the heart. Furthermore, cardiac Ucp3 and Cact mRNA was upregulated.ConclusionsLong-term treatment with the pan-PPAR agonist TTA or high-dose FO induced marked changes in PUFA composition and enzymatic activity involved in FA metabolism in the heart, different from liver. Changes included increased FA oxidation and a selective increase in cardiac n-3 PUFA.

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Section: Discussionsupporting

confidence: 90%

Long-term treatment with the pan-PPAR agonist tetradecylthioacetic acid or fish oil is associated with increased cardiac content of n-3 fatty acids in rat

et al. 2012

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“…Moreover, increased mRNA expression of CPT-1, CPT-2, CACT and HMGSC-1 indicated upregulation of mitochondrial fatty acid oxidation and ketogenesis. This was also associated with a significant increase in UCP3 expression, confirming previous results [27]. The upregulation of these factors, as well as ACOX-1, supports PPARα activation.…”

Section: Mitochondrial Biogenesis Coincides With Hypertrophy In Hepatsupporting

confidence: 89%

“…Activation of PPARα was confirmed by upregulated mRNA expression of ACOX, CPT II and UCP3, representing target genes of this transcription factor [27,28].…”

Section: Discussionmentioning

confidence: 91%

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Induction of mitochondrial biogenesis and respiration is associated with mTOR regulation in hepatocytes of rats treated with the pan-PPAR activator tetradecylthioacetic acid (TTA)

Hagland

Nilsson

Burri

et al. 2013

Biochemical and Biophysical Research Communications

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Word count: 4587 2 ABSTRACTThe hypolipidemic effect of peroxisome proliferator-activated receptor (PPAR) activators has been explained by increasing mitochondrial fatty acid oxidation, as observed in livers of rats treated with the pan-PPAR activator tetradecylthioacetic acid (TTA). PPAR-activation does, however, not fully explain the metabolic adaptations observed in hepatocytes after treatment with TTA. We therefore characterized the mitochondrial effects, and linked this to signalling by the metabolic sensor, the mammalian target of rapamycin (mTOR). In hepatocytes isolated from TTA-treated rats, the changes in cellular content and morphology were consistent with hypertrophy. This was associated with induction of multiple mitochondrial biomarkers, including mitochondrial DNA, citrate synthase and mRNAs of mitochondrial proteins.Transcription analysis further confirmed activation of PPARα-associated genes, in addition to genes related to mitochondrial biogenesis and function. Analysis of mitochondrial respiration revealed that the capacity of both electron transport and oxidative phosphorylation were increased. These effects coincided with activation of the stress related factor, ERK1/2, and mTOR. The protein level and phosphorylation of the downstream mTOR targets eIF4G and 4E-BP1 were induced. In summary, TTA increases hepatocyte respiration by inducing hypertrophy and mitochondrial biogenesis in rat, via adaptive regulation of PPARs as well as mTOR.

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“…Rat Liver Mitochondria-Enriched Fractions-Crude mitochondrial samples from 25 animals were generated in the group of Professor Rolf Kristian Berge, University of Bergen, Norway as recently described (18). The model sample was generated by pooling equal amounts of the 25 preparations.…”

Section: Methodsmentioning

confidence: 99%

Quantitative Assessment of In-solution Digestion Efficiency Identifies Optimal Protocols for Unbiased Protein Analysis

León

Schwämmle

Jensen

et al. 2013

Molecular & Cellular Proteomics

228

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The majority of mass spectrometry-based protein quantification studies uses peptide-centric analytical methods and thus strongly relies on efficient and unbiased protein digestion protocols for sample preparation. We present a novel objective approach to assess protein digestion efficiency using a combination of qualitative and quantitative liquid chromatography-tandem MS methods and statistical data analysis. In contrast to previous studies we employed both standard qualitative as well as data-independent quantitative workflows to systematically assess trypsin digestion efficiency and bias using mitochondrial protein fractions. We evaluated nine trypsin-based digestion protocols, based on standard in-solution or on spin filter-aided digestion, including new optimized protocols. We investigated various reagents for protein solubilization and denaturation (dodecyl sulfate, deoxycholate, urea), several trypsin digestion conditions (buffer, RapiGest, deoxycholate, urea), and two methods for removal of detergents before analysis of peptides (acid precipitation or phase separation with ethyl acetate). Our data-independent quantitative liquid chromatography-tandem MS workflow quantified over 3700 distinct peptides with 96% completeness between all protocols and replicates, with an average 40% protein sequence coverage and an average of 11 MS-based proteomics is an indispensable technology for the characterization of complex biological systems, including relative or absolute protein expression levels and protein post-translational modifications. The most popular method for analyzing medium to high complexity protein samples in large-scale proteomics relies on protein digestion by using the endoprotease trypsin. Analysis and sequencing of tryptic peptides by liquid chromatography-tandem MS (LC-MS/MS) 1 then enables identification and determination of protein expression levels based on the peptide ion abundance level or the (fragment) ion intensities of identified peptides. This peptide-centric approach thus strongly relies on efficient, unbiased and reproducible protein digestion protocols. Efficiency is required to maximize the number of detectable peptides per protein (coverage) to distinguish unique proteins within protein families with similar sequences and/or sequence variants, and to detect post-translational modifications. Unbiased generation of peptides is required for the resulting data set to most accurately reflect the relative (stoichiometry) and absolute protein abundance in a sample. A particular protocol should be unbiased with respect to abundance, molecular weight, hydrophobicity and protein class. Membrane proteins for example are often suspected to be underrepresented. For MS-based proteomics approaches several critical steps can be distinguished: (a) disruption and solubilization of cells and protein complexes, (b) protein denaturation and enzymatic proteolysis, (c) MS-compatible peptide recovery, which normally entails removal of reagent leftovers and desalting before MS analysis, (d) adequate pept...

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Fish oil and 3-thia fatty acid have additive effects on lipid metabolism but antagonistic effects on oxidative damage when fed to rats for 50 weeks

Cited by 31 publications

References 51 publications

Long-term treatment with the pan-PPAR agonist tetradecylthioacetic acid or fish oil is associated with increased cardiac content of n-3 fatty acids in rat

Long-term treatment with the pan-PPAR agonist tetradecylthioacetic acid or fish oil is associated with increased cardiac content of n-3 fatty acids in rat

Induction of mitochondrial biogenesis and respiration is associated with mTOR regulation in hepatocytes of rats treated with the pan-PPAR activator tetradecylthioacetic acid (TTA)

Quantitative Assessment of In-solution Digestion Efficiency Identifies Optimal Protocols for Unbiased Protein Analysis

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