Correction: Genome-wide association study of fish oil supplementation on lipid traits in 81,246 individuals reveals new gene-diet interaction loci.
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SUBMITTER: Francis M
PROVIDER: S-EPMC10112772 | biostudies-literature | 2023 Apr
REPOSITORIES: biostudies-literature
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Correction: Genome-wide association study of fish oil supplementation on lipid traits in 81,246 individuals reveals new gene-diet interaction loci.
Francis Michael M Li Changwei C Sun Yitang Y Zhou Jingqi J Li Xiang X Brenna J Thomas JT Ye Kaixiong K
PLoS genetics 20230418 4
[This corrects the article DOI: 10.1371/journal.pgen.1009431.]. ...[more]
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Project description:Fish oil supplementation is widely used for reducing serum triglycerides (TAGs) but has mixed effects on other circulating cardiovascular biomarkers. Many genetic polymorphisms have been associated with blood lipids, including high- and low-density-lipoprotein cholesterol (HDL-C, LDL-C), total cholesterol, and TAGs. Here, the gene-diet interaction effects of fish oil supplementation on these lipids were analyzed in a discovery cohort of up to 73,962 UK Biobank participants, using a 1-degree-of-freedom (1df) test for interaction effects and a 2-degrees-of-freedom (2df) test to jointly analyze interaction and main effects. Associations with P < 1×10-6 in either test (26,157; 18,300 unique variants) were advanced to replication in up to 7,284 participants from the Atherosclerosis Risk in Communities (ARIC) Study. Replicated associations reaching 1df P < 0.05 (2,175; 1,763 unique variants) were used in meta-analyses. We found 13 replicated and 159 non-replicated (UK Biobank only) loci with significant 2df joint tests that were predominantly driven by main effects and have been previously reported. Four novel interaction loci were identified with 1df P < 5×10-8 in meta-analysis. The lead variant in the GJB6-GJB2-GJA3 gene cluster, rs112803755 (A>G; minor allele frequency = 0.041), shows exclusively interaction effects. The minor allele is significantly associated with decreased TAGs in individuals with fish oil supplementation, but with increased TAGs in those without supplementation. This locus is significantly associated with higher GJB2 expression of connexin 26 in adipose tissue; connexin activity is known to change upon exposure to omega-3 fatty acids. Significant interaction effects were also found in three other loci in the genes SLC12A3 (HDL-C), ABCA6 (LDL-C), and MLXIPL (LDL-C), but highly significant main effects are also present. Our study identifies novel gene-diet interaction effects for four genetic loci, whose effects on blood lipids are modified by fish oil supplementation. These findings highlight the need and possibility for personalized nutrition.
| S-EPMC8021161 | biostudies-literature
Project description:Double-blind, randomized clinical trial to assess the effects of 1,55 g/day of n-3 fatty acids from fish oil concomitant chemotherapy in gastrointestinal cancer.
| 2209534 | ecrin-mdr-crc
Project description:Colorectal cancer is the second leading cause of cancer-related death within the United States. Animal models and observational studies have suggested that marine-derived n-3 polyunsaturated fatty acids [PUFA] such as eicosapentanoic acid [EPA] and docosahexanoic acid [DHA] may reduce the risk of colorectal cancer. In addition, it may be the relative proportion of n-3 to n-6 PUFAs that best determines the chemopreventive effects of fish oils. This ratio is important because the n-6 PUFA, arachidonic acid (ARA), is converted via the cyclo-oxygenase (COX) pathway to prostaglandin E2 (PGE2), an inflammatory eicosanoid overproduced in colorectal neoplasms while EPA is converted to the anti-inflammatory prostaglandin E3 (PGE3). While the ratio of n-6 to n-3 PUFAs can be altered through dietary changes, genetic factors may also influence this ratio. Recent genetic studies have demonstrated that much of the tissue levels of ARA is determined by differences in a gene called fatty acid desaturase 1 (FADS1). FADS1 is the rate-limiting enzyme in the conversion of linoleic acid, the most commonly consumed PUFA in the Western diet, to ARA, and one particular genetic variant caller rs174537 is associated with lower fatty acid desaturase activity and subsequently lower tissue levels of ARA.
The study hypothesis is that individuals with genetically determined lower activity of FADS1 will derive greater benefit from fish oil supplementation than individuals with higher FADS1 activity because of lower tissue levels of ARA and subsequently a more favorable n-6 to n-3 PUFA ratio. To test this hypothesis the investigators will recruit 150 participants with recently identified adenomatous polyps and conduct a 6-month double blind 3 X 2 factorial randomized controlled trial. The first factor will be FADS1 genotype (GG, GT, and TT) and the second factor will be fish oil supplementation (fish oil versus placebo). The primary outcome will be the change in rectal epithelial cell growth and cell death. Secondary outcomes will include rectal epithelial cell expression of genes important in PGE2 production, rectal cell production of PGE2 and PGE3, rectal mucosal tissue levels of fatty acids, and changes in biomarkers of inflammation (C-reactive protein), adipokines (leptin, adiponectin), and markers of insulin sensitivity.
The specific aims include: 1) to determine the efficacy of fish oil supplements on rectal epithelial cell proliferation indexes and markers of rectal crypt apoptosis, and 2) to determine the effect of genetically-determined fatty acid desaturase 1 activity on fish oil supplementation for colorectal cancer chemoprevention. The investigators long-term objectives are to determine genetic factors that might influence the efficacy of fish oil supplementation in order to conduct a more definitive adenoma recurrence trial using marine-derived n-3 PUFAs. The investigators anticipate that fish oil will have anti-neoplastic effect and individuals with low FADS1 activity will have a greater response compared to individuals with high FADS1 activity
| 2130139 | ecrin-mdr-crc
Project description:Abstract Objectives To identify genetic variants that modify the effect of fish oil supplementation on blood lipids, including low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), total cholesterol, and triglycerides. Methods We performed a genome-wide interaction study in 73,962 participants of European ancestry from the UK Biobank. Candidate associations were evaluated in a replication study with 7,284 participants from the Atherosclerosis Risk in Communities (ARIC) Study. Meta-analysis was further performed across the two cohorts. Results Four novel interaction loci were identified at genome-wide significance in meta-analysis. The lead variant in the GJB6-GJB2-GJA3 gene cluster, rs112803755 (A > G; minor allele frequency = 0.041), shows an interaction effect but not the main effect, suggesting that it would not have been discovered in a typical association study. Fish oil supplementation is associated with a decreased blood level of triglycerides in individuals carrying the minor allele, but with an increased level in homozygotes of the major allele. This locus is significantly associated with higher GJB2 expression of connexin 26 in adipose tissue, while connexin activity is known to change upon exposure to omega-3 fatty acids. Significant interaction effects were also found in three other loci in the genes SLC12A3 (HDL-C), ABCA6 (LDL-C), and MLXIPL (LDL-C), but highly significant main effects are also present. Conclusions Our study identifies novel interaction effects for four genetic loci and highlights genetic variants in the GJB6-GJB2-GJA3 gene cluster, which modify the effects of fish oil supplementation on lowering blood triglycerides. These findings highlight the need and possibility for personalized nutrition. Funding Sources The University of Georgia Research Foundation
| S-EPMC8181881 | biostudies-literature
Project description:ObjectiveLittle is known about the effects of over-the-counter fish oil (FO) supplements on circulating omega-3 polyunsaturated fatty acid (n-3 PUFA)-derived specialized pro-resolving mediators (SPMs), nor about whether having a chronic inflammatory disease such as rheumatoid arthritis (RA) influences SPM levels. We investigated associations between over-the-counter n-3 PUFA FO supplementation and circulating SPMs among patients with vs. without RA.MethodsWe studied 104 participants: 26 with RA taking FO matched by age and sex to 26 with RA not taking FO, 26 without RA taking FO, and 26 without RA not taking FO. Targeted-liquid chromatography-tandem mass spectroscopy was performed on patient plasma to identify and quantify 27 lipid mediators (including eicosanoids and SPMs). We performed t-tests and then multivariable linear regression analyses to assess whether having RA or taking FO supplements was associated with circulating lipid mediator concentrations, adjusting for age, race, sex, smoking, body mass index, and current medication use (statins, prednisone and immunomodulators among RA cases only). We tested for interactions between FO supplementation and RA status. We also conducted Spearman's correlations between EPA, DHA, and ARA and their downstream metabolites.ResultsAmong patients who were taking FO compared to those who were not, in multivariable- adjusted analyses, SPM substrates EPA and DHA were both elevated as were several of their pro-resolving bioactive products, including 15- and 18-HEPE from EPA, and 14- and 17-HDHA from DHA, which are substrates for specific SPMs. While E-series and D-series resolvins were present and identified, we did not find statistical elevations of other SPMs. Results were similar among patients with RA and patients without RA, taking vs. not taking FO supplementation (no formal statistical interaction observed). There was a strong positive correlation between EPA and DHA and their immediate downstream SPM precursors (18-HEPE and15-HEPE from EPA; 17-HDHA and 14-HDHA from DHA) among all patients.ConclusionPatients taking FO supplements, regardless of RA status, not only had higher blood levels of EPA and DHA, but also of their enzymatic products 18-HEPE (E-series resolvin precursors), 15-HEPE and 17-HDHA (D-series resolvin and protectin precursors). Patients with RA, an inflammatory autoimmune disease, may be able to augment some SPM precursor reserves, similarly to matched controls without RA, by taking oral FO supplements.
| S-EPMC10027850 | biostudies-literature
Project description:Pre-pregnancy obesity is a contributing factor for impairments in offspring metabolic health. Interventional strategies during pregnancy are a potential approach to alleviate and/or prevent obesity and obesity related metabolic alterations in the offspring. Fish oil (FO), rich in omega-3 polyunsaturated fatty acids (n-3 PUFAs) exerts metabolic health benefits. However, the role of FO in early life remains still unknown. Hence, this study objective was to determine the effect of FO supplementation in mice from pre-pregnancy through lactation, and to study the post-natal metabolic health effects in gonadal fat and liver of offspring fed high fat (HF) diet with or without FO. Female C57BL6J mice aged 4-5 weeks were fed a HF (45% fat) diet supplemented with or without FO (30 g/kg of diet) and low fat (LF; 10% fat) pre-pregnancy through lactation. After weaning, offspring (male and female) from HF or FO dams either continued the same diet (HF-HF and FO-FO) or switched to the other diet (HF-FO and FO-HF) for 13 weeks, creating four groups of treatment, and LF-LF was used as a control group. Serum, gonadal fat and liver tissue were collected at termination for metabolic analyses. Offspring of both sexes fed HF with or without fish oil gained (p < 0.05) more weight post weaning, compared to LF-LF-fed mice. All the female offspring groups supplemented with FO had reduced body weight compared to the respective male groups. Further, FO-FO supplementation in both sexes (p < 0.05) improved glucose clearance and insulin sensitivity compared to HF-HF. All FO-FO fed mice had significantly reduced adipocyte size compared to HF-HF group in both male and females. Inflammation, measured by mRNA levels of monocyte chemoattractant protein 1 (Mcp1), was reduced (p < 0.05) with FO supplementation in both sexes in gonadal fat and in the liver. Markers of fatty acid synthesis, fatty acid synthase (Fasn) showed no sex specific differences in gonadal fat and liver of mice supplemented with HF. Female mice had lower liver triglycerides than male counterparts. Supplementation of FO in mice improved metabolic health of offspring by lowering markers of lipid synthesis and inflammation.
| S-EPMC8625698 | biostudies-literature
Project description:Increasing energy expenditure (EE) is beneficial for preventing obesity. Diet-induced thermogenesis (DIT) is one of the components of total EE. Therefore, increasing DIT is effective against obesity. We examined how much fish oil (FO) increased DIT by measuring absolute values of DIT in mice. C57BL/6J male mice were given diets of 30 energy% fat consisting of FO or safflower oil plus butter as control oil (Con). After administration for 9 days, respiration in mice was monitored, and then the data were used to calculate DIT and EE. DIT increased significantly by 1.2-fold in the FO-fed mice compared with the Con-fed mice. Body weight gain was significantly lower in the FO-fed mice. FO increased the levels of uncoupling protein 1 (Ucp1) mRNA and UCP1 protein in brown adipose tissue (BAT) by 1.5- and 1.2-fold, respectively. In subcutaneous white adipose tissue (subWAT), the levels of Ucp1 mRNA and UCP1 protein were increased by 6.3- and 2.7-fold, respectively, by FO administration. FO also significantly increased the expression of markers of browning in subWAT such as fibroblast growth factor 21 and cell death-inducing DNA fragmentation factor α-like effector a. Thus, dietary FO seems to increase DIT in mice via the increased expressions of Ucp1 in BAT and induced browning of subWAT. FO might be a promising dietary fat in the prevention of obesity by upregulation of energy metabolism.
| S-EPMC8156710 | biostudies-literature
Project description:Resolution of parenteral nutrition-associated liver disease has been identified in infants receiving SMOFlipid™ or a 100% fish oil lipid emulsion (FOLE). However, the effect of FOLE is unknown when the previous emulsion received is a mixed lipid emulsion containing fish oil. This observational pilot study reports data regarding the use of Omegaven™ after the diagnosis of cholestasis while receiving SMOFlipid™. We conducted a retrospective review of medical charts of neonates in which a partially fish oil-based lipid emulsion was replaced by a fish oil lipid emulsion at 1 g/kg/day due to cholestasis. Thirty-eight infants (92.1% preterm, being 44.7% born below 28 weeks' gestation), received FOLE. Birth weight was 1390 (743.0; 2298) grams. The age that cholestasis diagnosed was 15.0 (10.0; 24.8) days. The fish oil emulsion was administered for 38.5 (11.2; 51.8) days. In 73.7% (28/38) of the neonates, the cholestasis was resolved. In 34.2% (13/38), resolution happened before FOLE discontinuation. In addition, in the rest of the neonates (15) in whom cholestasis resolved, resolution occurred after FOLE discontinuation. Nine of the neonates died. In conclusion, the use of a 100% fish oil-based emulsion in neonates afflicted with cholestasis developed while on a partially fish oil-based emulsion is associated with a bilirubin decrease.
| S-EPMC9920606 | biostudies-literature
Project description:Preclinical studies suggest lowering dietary fat and decreasing the ratio of omega-6 to omega-3 polyunsaturated fatty acids decreases the risk of prostate cancer development and progression. We conducted a phase II randomized trial to test the effect of decreasing dietary fat combined with decreasing the dietary omega-6:omega-3 ratio on biomarkers related to prostate cancer development and progression. Patients undergoing radical prostatectomy were randomly assigned to receive a low-fat diet with 5 grams of fish oil daily (dietary omega-6:omega-3 ratio of 2:1) or a control Western diet (omega-6:omega-3 ratio of 15:1) for four to six weeks prior to surgery. The primary endpoint was change in serum insulin-like growth factor I (IGF-1) between arms. Secondary endpoints were serum IGFBP-1, prostate prostaglandin E2 levels, omega-6:omega-3 fatty acid ratios, COX-2, and markers of proliferation and apoptosis. Fifty-five patients were randomized and 48 completed the trial. There was no treatment difference in the primary outcome. Positive secondary outcomes in the low-fat fish oil versus Western group were reduced benign and malignant prostate tissue omega-6:omega-3 ratios, reduced proliferation (Ki-67 index), and reduced proliferation in an ex vivo bioassay when patient sera was applied to prostate cancer cells in vitro. In summary, four to six weeks of a low-fat diet and fish oil capsules to achieve an omega-6:omega-3 fatty acid ratio of 2:1 had no effect on serum IGF-1 levels, though in secondary analyses, the intervention resulted in decreased prostate cancer proliferation and decreased prostate tissue omega-6:omega-3 ratios. These results support further studies evaluating reduction of dietary fat with fish oil supplementation on modulating prostate cancer biology.
| S-EPMC3232341 | biostudies-literature
Project description:BackgroundWe recently demonstrated that maternal dietary supplementation with fish oil-derived n-3 long-chain polyunsaturated fatty acids (n-3 LCPUFAs) during pregnancy reduces the risk of asthma in the offspring but the mechanisms involved are unknown.MethodsHere we investigated potential metabolic mechanisms using untargeted liquid chromatography-mass spectrometry-based metabolomics on 577 plasma samples collected at age 6 months in the offspring of mothers participating in the n-3 LCPUFA randomized controlled trial. First, associations between the n-3 LCPUFA supplementation groups and child metabolite levels were investigated using univariate regression models and data-driven partial least square discriminant analyses (PLS-DA). Second, we analyzed the association between the n-3 LCPUFA metabolomic profile and asthma development using Cox-regression. Third, we conducted mediation analyses to investigate whether the protective effect of n-3 LCPUFA on asthma was mediated via the metabolome.FindingsThe univariate analyses and the PLS-DA showed that maternal fish oil supplementation affected the child's metabolome, especially with lower levels of the n-6 LCPUFA pathway-related metabolites and saturated and monounsaturated long-chain fatty acids-containing compounds, lower levels of metabolites of the tryptophan pathway, and higher levels of metabolites in the tyrosine and glutamic acid pathway. This fish oil-related metabolic profile at age 6 months was significantly associated with a reduced risk of asthma by age 5 and the metabolic profile explained 24% of the observed asthma-protective effect in the mediation analysis.InterpretationSeveral of the observed pathways may be involved in the asthma-protective effect of maternal n-3 LCPUFA supplementation and act as mediators between the intervention and disease development.FundingCOPSAC is funded by private and public research funds all listed on www.copsac.com.
| S-EPMC6712349 | biostudies-literature