Protein synthesis and degradation in isolated muscle. Effect of omega 3 and omega 6 fatty acids.
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ABSTRACT:
SUBMITTER: Palmer RM
PROVIDER: S-EPMC1147750 | biostudies-other | 1987 Mar
REPOSITORIES: biostudies-other
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Project description:Polyunsaturated fatty acids (PUFAs) are essential dietary components. They are not only used for energy, but also act as signaling molecules. The delta-6 desaturase (D6D) enzyme, encoded by the FADS2 gene, is one of two rate limiting enzymes that convert the PUFA precursors - ?-linolenic (n-3) and linoleic acid (n-6) to their respective metabolites. Alterations in the D6D enzyme activity alters fatty acid profiles and are associated with metabolic and inflammatory diseases including cardiovascular disease and type 2 diabetes. Omega-3 PUFAs, specifically its constituent fatty acids DHA and EPA, are known for their anti-inflammatory ability and are also beneficial in the prevention of skeletal muscle wasting, however the mechanism for muscle preservation is not well understood. Moreover, little is known of the effects of altering the n-6/n-3 ratio in the context of a high-fat diet, which is known to downregulate protein synthesis. Twenty C57BL6 male mice were fed a high-fat lard (HFL, 45% fat (mostly lard), 35% carbohydrate and 20% protein, n-6:n-3 PUFA, 13:1) diet for 6 weeks. Mice were then divided into 4 groups (n = 5 per group): HFL- , high-fat oil- (HFO, 45% fat (mostly Menhaden oil), 35% carbohydrate and 20% protein, n-6:n-3 PUFA, 1:3), HFL+ (HFL diet plus an orally administered FADS2 inhibitor, 100 mg/kg/day), and HFO+ (HFO diet plus an orally administered FADS2 inhibitor, 100 mg/kg/day). After 2 weeks on their respective diets and treatments, animals were sacrificed and gastrocnemius muscle harvested. Protein turnover signaling were analyzed via Western Blot. 4-EBP1 and ribosomal protein S6 expression were measured. A two-way ANOVA revealed no significant change in the phosphorylation of both 4EBP-1 and ribosomal protein S6 with diet or inhibitor. There was a significant reduction in STAT3 phosphorylation with the inhibition of FADS2 (p = 0.03). Additionally, we measured markers of protein degradation through levels of FOXO phosphorylation, ubiquitin, and LC3B expression; there was a trend towards increased phosphorylation of FOXO (p = 0.08) and ubiquitinated proteins (p = 0.05) with FADS2 inhibition. LC3B expression, a marker of autophagy, was significantly higher in the HFL plus FADS2 inhibition group from all other comparisons. Lastly, we analyzed activation of mitochondrial biogenesis which is closely linked with protein synthesis through PGC1-? and Cytochrome-C expression, however no significant differences were associated with either marker across all groups. Collectively, these data suggest that the protective effects of muscle mass by omega-3 fatty acids are from inhibition of protein degradation. Our aim was to determine the role of PUFA metabolites, DHA and EPA, in skeletal muscle protein turnover and assess the effects of n-3s independently. We observed that by inhibiting the FADS2 enzyme, the protective effect of n-3s on protein synthesis and proliferation was lost; concomitantly, protein degradation was increased with FADS2 inhibition regardless of diet.
| S-EPMC6424014 | biostudies-literature
Project description:The optimal ratio of omega-6 to omega-3 polyunsaturated fatty acids (PUFAs) is important for keeping homeostasis of biological processes and metabolism, yet the underlying biological mechanism is poorly understood. The objective of this study was to identify changes in the pig liver transcriptome induced by a diet enriched with omega-6 and omega-3 fatty acids, and to characterize the biological mechanisms related to PUFA metabolism. Polish Landrace pigs (n =12) were fed diet enriched with linoleic acid (LA, omega-6) and alpha-linolenic acid (ALA, omega-3 family) or standard diet as a control. The fatty acids profiling was assayed in order to verify how feeding influenced the fatty acids content in liver, and subsequently next-generation sequencing (NGS) was used to identify differentially expressed genes (DEG) between transcriptomes between dietary groups. The biological mechanisms and pathway interaction networks were identified by analysis in DAVID and Cytoscape tools. Fatty acids profile analysis indicated a higher contribution of PUFAs in liver for LA and ALA-enriched diet group, particularly for the omega-3 fatty acids family, but not omega-6. Next-generation sequencing identified 3,565 DEG, 1,484 of which were induced and 2,081 were suppressed by PUFA supplemenation. Low ratio of omega-6/-3 fatty acids resulted in modulation of fatty acids metabolism pathways and over-representation of genes involved in membrane composition, signal transduction and immune response pathways. In conclusion, a diet enriched with omega-6 and omega-3 fatty acids altered the transcriptomic profile of the pig liver and affected a set of genes involved in metabolic pathways important to animal health status. Hepatic mRNA profiles of Polish Landrace pig breed fed two different diets, were generated by deep sequencing, using Illumina MiSeq. Experimental diet was enriched with polyunsaturated fatty acids (omega-6 and omega-3), while standard diet remain as a cotrol. 2 pooled samples each containing RNA extracts from 6 individuals livers were analyzed.
2016-03-15 | E-GEOD-72123 | biostudies-arrayexpress
Project description:Omega-3 polyunsaturated fatty acids (n3-PUFA) are recognized for their anti-inflammatory effects and may be beneficial in the context of sarcopenia. We determined the influence of n3-PUFA on muscle mitochondrial physiology and protein metabolism in older adults. Twelve young (18-35 years) and older (65-85 years) men and women were studied at baseline. Older adults were studied again following n3-PUFA supplementation (3.9g/day, 16 weeks). Muscle biopsies were used to evaluate respiratory capacity (high resolution respirometry) and oxidant emissions (spectrofluorometry) in isolated mitochondria. Maximal respiration was significantly lower in older compared to young. n3-PUFA did not change respiration, but significantly reduced oxidant emissions. Participants performed a single bout of resistance exercise, followed by biopsies at 15 and 18 hours post exercise. Several genes involved in muscle protein turnover were significantly altered in older adults at baseline and following exercise, yet muscle protein synthesis was similar between age groups under both conditions. Following n3-PUFA supplementation, mixed muscle, mitochondrial, and sarcoplasmic protein synthesis rates were increased in older adults before exercise. n3-PUFA increased post-exercise mitochondrial and myofibrillar protein synthesis in older adults. These results demonstrate that n3-PUFA reduce mitochondrial oxidant emissions, increase postabsorptive muscle protein synthesis, and enhance anabolic responses to exercise in older adults.
| S-EPMC5425117 | biostudies-literature
Project description:Omega-3 long-chain polyunsaturated fatty acids (LC-PUFAs), such as eicosapentaenoic acid (EPA) (20:5n-3) and docosahexaenoic acid (DHA) (22:6n-3), are considered essential for human health. Microorganisms are the primary producers of omega-3 fatty acids in marine ecosystems, representing a sustainable source of these lipids, as an alternative to the fish industry. Some marine bacteria can produce LC-PUFAs de novo via the Polyunsaturated Fatty Acid (Pfa) synthase/ Polyketide Synthase (PKS) pathway, which does not require desaturation and elongation of saturated fatty acids. Cultivation-independent surveys have revealed that the diversity of microorganisms harboring a molecular marker of the pfa gene cluster (i.e., pfaA-KS domain) is high and their potential distribution in marine systems is widespread, from surface seawater to sediments. However, the isolation of PUFA producers from marine waters has been typically restricted to deep or cold environments. Here, we report a phenotypic and genotypic screening for the identification of omega-3 fatty acid producers in free-living bacterial strains isolated from 5, 500, and 1000 m deep coastal seawater from the Bay of Biscay (Spain). We further measured EPA production in pelagic Vibrio sp. strains collected at the three different depths. Vibrio sp. EPA-producers and non-producers were simultaneously isolated from the same water samples and shared a high percentage of identity in their 16S rRNA genes, supporting the view that the pfa gene cluster can be horizontally transferred. Within a cluster of EPA-producers, we found intraspecific variation in the levels of EPA synthesis for isolates harboring different genetic variants of the pfaA-KS domain. The maximum production of EPA was found in a Vibrio sp. strain isolated from a 1000 m depth (average 4.29% ± 1.07 of total fatty acids at 10 °C, without any optimization of culturing conditions).
| S-EPMC7074563 | biostudies-literature
Project description:The optimal ratio of omega-6 to omega-3 polyunsaturated fatty acids (PUFAs) is important for keeping homeostasis of biological processes and metabolism, yet the underlying biological mechanism is poorly understood. The objective of this study was to identify changes in the pig liver transcriptome induced by a diet enriched with omega-6 and omega-3 fatty acids, and to characterize the biological mechanisms related to PUFA metabolism. Polish Landrace pigs (n =12) were fed diet enriched with linoleic acid (LA, omega-6) and alpha-linolenic acid (ALA, omega-3 family) or standard diet as a control. The fatty acids profiling was assayed in order to verify how feeding influenced the fatty acids content in liver, and subsequently next-generation sequencing (NGS) was used to identify differentially expressed genes (DEG) between transcriptomes between dietary groups. The biological mechanisms and pathway interaction networks were identified by analysis in DAVID and Cytoscape tools. Fatty acids profile analysis indicated a higher contribution of PUFAs in liver for LA and ALA-enriched diet group, particularly for the omega-3 fatty acids family, but not omega-6. Next-generation sequencing identified 3,565 DEG, 1,484 of which were induced and 2,081 were suppressed by PUFA supplemenation. Low ratio of omega-6/-3 fatty acids resulted in modulation of fatty acids metabolism pathways and over-representation of genes involved in membrane composition, signal transduction and immune response pathways. In conclusion, a diet enriched with omega-6 and omega-3 fatty acids altered the transcriptomic profile of the pig liver and affected a set of genes involved in metabolic pathways important to animal health status.
2016-03-15 | GSE72123 | GEO
Project description:Kidney function gradually decreases with age, and myocardial infarction accelerates this deterioration. Omega-3 (n-3) fatty acids may slow down the decline of kidney function. The effect of marine and plant-derived n-3 fatty acids on kidney function in patients after myocardial infarction was examined.In the Alpha Omega Trial, 2344 patients with history of myocardial infarction ages 60-80 years old (81% men) were randomized to one of four trial margarines. The patients received an additional targeted amount of 400 mg/d eicosapentaenoic acid and docosahexaenoic acid, 2 g/d ?-linolenic acid, eicosapentaenoic acid-docosahexaenoic acid plus ?-linolenic acid, or placebo for 40 months. Serum cystatin C and serum creatinine were assessed at baseline and after 40 months. Creatinine-cystatin C-based GFR was estimated with the Chronic Kidney Disease Epidemiology Collaboration equation.Patients consumed 19.9 g margarine/d, providing an additional 239 mg/d eicosapentaenoic acid with 159 mg/d docosahexaenoic acid, 1.99 g/d ?-linolenic acid, or both in the active treatment groups. After 40 months, compared with baseline, mean (±SD) creatinine-cystatin C-based GFR was -6.9 (±12.6), -4.8 (±13.4), -6.2 (±12.8), and -6.0 (±13.0) ml/min per 1.73 m(2) in the placebo, eicosapentaenoic acid-docosahexaenoic acid, ?-linolenic acid, and eicosapentaenoic acid-docosahexaenoic acid plus ?-linolenic acid groups, respectively. After 40 months, in patients receiving eicosapentaenoic acid-docosahexaenoic acid compared with placebo, the decline in creatinine-cystatin C-based GFR was 2.1 less (95% confidence interval, 0.6 to 3.6; P<0.01) ml/min per 1.73 m(2); other comparisons were not statistical significant. Odds ratios (95% confidence intervals) of incident CKD (<60 ml/min per 1.73 m(2)) and rapid decline of kidney function (?3 ml/min per year) for eicosapentaenoic acid-docosahexaenoic acid compared with placebo were 0.83 (0.58 to 1.18) and 0.85 (0.67 to 1.08), respectively.Long-term supplementation with 400 mg/d eicosapentaenoic acid-docosahexaenoic acid provides a small beneficial effect on kidney function in patients with a history of myocardial infarction.
| S-EPMC4186521 | biostudies-literature
Project description:More than a dozen epidemiological studies have reported that reduced levels or intake of omega-3 fatty acids or fish consumption is associated with increased risk for age-related cognitive decline or dementia such as Alzheimer's disease (AD). Increased dietary consumption or blood levels of docosahexaenoic acid (DHA) appear protective for AD and other dementia in multiple epidemiological studies; however, three studies suggest that the ApoE4 genotype limits protection. DHA is broadly neuroprotective via multiple mechanisms that include neuroprotective DHA metabolites, reduced arachidonic acid metabolites, and increased trophic factors or downstream trophic signal transduction. DHA is also protective against several risk factors for dementia including head trauma, diabetes, and cardiovascular disease. DHA is specifically protective against AD via additional mechanisms: It limits the production and accumulation of the amyloid beta peptide toxin that is widely believed to drive the disease; and it also suppresses several signal transduction pathways induced by Abeta, including two major kinases that phosphorylate the microtubule-associated protein tau and promote neurofibrillary tangle pathology. Based on the epidemiological and basic research data, expert panels have recommended the need for clinical trials with omega-3 fatty acids, notably DHA, for the prevention or treatment of age-related cognitive decline--with a focus on the most prevalent cause, AD. Clinical trials are underway to prevent and treat AD. Results to-date suggest that DHA may be more effective if it is begun early or used in conjunction with antioxidants.
| S-EPMC4019002 | biostudies-literature
Project description:Intervention 1: Intervention 1: a 50000 IU vitamin D tablet (Zahravi, Iran), weekly+ 2 omega-3 fatty acid capsules (each capsule containing 330 mg omega-3 fatty acid) (Minami Nutrition, Belgium), daily, for 8 weeks. Intervention 2: Intervention group 2: a 50000 IU vitamin D tablet (Zahravi, Iran), weekly+ 2 omega-3 fatty acid placebo (Zahravi, Iran), daily, for 8 weeks. Intervention 3: Intervention group 3: two omega-3 fatty acid capsules (each capsule containing 330 mg omega-3 fatty acid) (Minami Nutrition, Belgium), daily+ a vitamin D placebo (Zahravi, Iran), weekly, for 8 weeks. Intervention 4: Control group: a vitamin D placebo (Zahravi, Iran), weekly+ 2 omega-3 fatty acid placebo (Zahravi, Iran), daily, for 8 weeks.
Primary outcome(s): Serum level of TNF-a. Timepoint: Before and 8 weeks after intervention. Method of measurement: Serum TNF-a levels will be assessed by ELISA and Bender Med kit (Bender Med, Germany).
Study Design: Randomization: Randomized, Blinding: Double blinded, Placebo: Used, Assignment: Factorial, Purpose: Treatment, Randomization description: For randomized allocation performing, permuted block randomization will be used by quadrilateral blocks. According to the sample size of 80 subjects, 20 blocks will be generated using the online site (www.sealedenvelope.com). In order to allocation concealment in the randomized process, unique codes will be used on the drug boxes that is generated by the software. Participants will enter based on the sequence produced into study and the drug packets with code registered will allocate to the individual. Therefore, before participants selection, they will be unaware of the type of intervention that will receive, as well as a random sequence produced during the study will be immune from prediction, Blinding description: For blinding, a person who is not involved in study protocol created the randomization list assigning participants to the vit
| 2475288 | ecrin-mdr-crc
Project description:The optimal ratio of omega-6 to omega-3 polyunsaturated fatty acids (PUFAs) is important for keeping the homeostasis of biological processes and metabolism, yet the underlying biological mechanism is poorly understood. The objective of this study was to identify changes in the pig liver transcriptome induced by a diet enriched with omega-6 and omega-3 fatty acids and to characterize the biological mechanisms related to PUFA metabolism. Polish Landrace pigs (n = 12) were fed diet enriched with linoleic acid (LA, omega-6) and α-linolenic acid (ALA, omega-3) or standard diet as a control. The fatty acid profiling was assayed in order to verify how feeding influenced the fatty acid content in the liver, and subsequently next-generation sequencing (NGS) was used to identify differentially expressed genes (DEG) between transcriptomes between dietary groups. The biological mechanisms and pathway interaction networks were identified using DAVID and Cytoscape tools. Fatty acid profile analysis indicated a higher contribution of PUFAs in the liver for LA- and ALA-enriched diet group, particularly for the omega-3 fatty acid family, but not omega-6. Next-generation sequencing identified 3565 DEG, 1484 of which were induced and 2081 were suppressed by PUFA supplementation. A low ratio of omega-6/omega-3 fatty acids resulted in the modulation of fatty acid metabolism pathways and over-representation of genes involved in energy metabolism, signal transduction, and immune response pathways. In conclusion, a diet enriched with omega-6 and omega-3 fatty acids altered the transcriptomic profile of the pig liver and would influence animal health status.
| S-EPMC4959555 | biostudies-literature
Project description:There is increasing evidence showing the role of fatty acids and their derived lipid intermediates in the regulation of skeletal muscle mass synthesis and function. However, the role of omega-3 fatty acids remains unclear. Therefore, we conducted a meta-analysis to evaluate the potential effects of omega-3 fatty acids on sarcopenia-related performances among the elderly. Eligible literature and reports of randomized controlled trials were comprehensively searched from the PubMed, Cochrane Library, ClinicalTrials.gov, and Cumulative Index to Nursing and Allied Health Literature (CINAHL) databases until July 2018. A total of 10 articles were available for the meta-analysis. There were minor benefits for muscle mass gain (0.33 kg; 95% CI: 0.05, 0.62) and timed up and go performance (-0.30 s; 95% CI: -0.43, -0.17). Subgroup analyses regarding muscle mass and walk speed indicated that omega-3 fatty acid supplements at more than 2 g/day may contribute to muscle mass gain (0.67 kg; 95% CI: 0.16, 1.18) and improve walking speed, especially for those receiving more than 6 months of intervention (1.78 m/sec; 95% CI: 1.38, 2.17). Our findings provide some insight into the effects of omega-3 fatty acids on muscle mass, especially for those taking supplements at more than 2 g/day. We also observed that a long period of omega-3 fatty acids supplementation may improve walking speed.
| S-EPMC7761957 | biostudies-literature