The effects of fenofibrate and fish oil on gene expression in peripheral blood mononuclear cells, muscle, and adipose tissue from overweight and obese individuals
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ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE27387 | GEO | 2025/02/01
REPOSITORIES: GEO
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Project description:The molecular effects of the non-selective dietary PPARalpha agonists n-3 LCPUFAs were compared side-by-side with those of the selective synthetic PPARalpha agonist fenofibrate on whole-genome gene expression in peripheral blood mononuclear cells (PBMCs), white adipose tissue (WAT), and muscle in overweight and obese subjects. Eleven overweight and obese subjects participated in a randomized, double-blind, placebo-controlled intervention trial and received in random order 3.7 g/d n-3 fatty acids (providing 1.7 g/d EPA and 1.2 g/d DHA), 200 mg fenofibrate or placebo treatment for 6 weeks separated by a wash-out period of at least 2-weeks. Fenofibrate changed 5 of the analysed 64 PPARalpha target genes in PBMC, 4 in muscle, and 2 in WAT, whereas fish oil changed 2 genes in WAT only. Both treatments changed 17 out of 25 similar pathways in PBMCs, related to xenobiotic metabolism, biosynthesis of steroids, lipid metabolism, transcription, proteasome function, Th1 immunity, propanoate metabolism and nucleotide metabolism. The majority (18 out of 25) of downregulated pathways in WAT were similarly changed in PBMCs after fish oil and related to lipid metabolism and amino acid metabolism. Fenofibrate and fish oil hardly affected pathways in muscle. In PBMCs, fenofibrate and fish oil only regulated 9 similar genes in metabolic syndrome-related pathways, which were IL25, TICAM1, PRDX2, PTGS1, AGK, FDPS, LDLR, TNNI3, LMAN1 and PTGS1. Overall, 6-weeks treatment with n-3 LCPUFAs and fenofibrate hardly affected PPARalpha target genes in overweight and obese subjects. Pathway analyses suggested that gene expression profiles in PBMCs can provide information about regulated metabolic processes by fish oil and fenofibrate in WAT, but not muscle. Expression of the individual genes, however, hardly overlapped between the tissues.
2025-02-01 | GSE27386 | GEO
Project description:The molecular effects of the non-selective dietary PPARalpha agonists n-3 LCPUFAs were compared side-by-side with those of the selective synthetic PPARalpha agonist fenofibrate on whole-genome gene expression in peripheral blood mononuclear cells (PBMCs), white adipose tissue (WAT), and muscle in overweight and obese subjects. Eleven overweight and obese subjects participated in a randomized, double-blind, placebo-controlled intervention trial and received in random order 3.7 g/d n-3 fatty acids (providing 1.7 g/d EPA and 1.2 g/d DHA), 200 mg fenofibrate or placebo treatment for 6 weeks separated by a wash-out period of at least 2-weeks. Fenofibrate changed 5 of the analysed 64 PPARalpha target genes in PBMC, 4 in muscle, and 2 in WAT, whereas fish oil changed 2 genes in WAT only. Both treatments changed 17 out of 25 similar pathways in PBMCs, related to xenobiotic metabolism, biosynthesis of steroids, lipid metabolism, transcription, proteasome function, Th1 immunity, propanoate metabolism and nucleotide metabolism. The majority (18 out of 25) of downregulated pathways in WAT were similarly changed in PBMCs after fish oil and related to lipid metabolism and amino acid metabolism. Fenofibrate and fish oil hardly affected pathways in muscle. In PBMCs, fenofibrate and fish oil only regulated 9 similar genes in metabolic syndrome-related pathways, which were IL25, TICAM1, PRDX2, PTGS1, AGK, FDPS, LDLR, TNNI3, LMAN1 and PTGS1. Overall, 6-weeks treatment with n-3 LCPUFAs and fenofibrate hardly affected PPARalpha target genes in overweight and obese subjects. Pathway analyses suggested that gene expression profiles in PBMCs can provide information about regulated metabolic processes by fish oil and fenofibrate in WAT, but not muscle. Expression of the individual genes, however, hardly overlapped between the tissues.
2025-02-01 | GSE27385 | GEO
Project description:The molecular effects of the non-selective dietary PPARalpha agonists n-3 LCPUFAs were compared side-by-side with those of the selective synthetic PPARalpha agonist fenofibrate on whole-genome gene expression in peripheral blood mononuclear cells (PBMCs), white adipose tissue (WAT), and muscle in overweight and obese subjects. Eleven overweight and obese subjects participated in a randomized, double-blind, placebo-controlled intervention trial and received in random order 3.7 g/d n-3 fatty acids (providing 1.7 g/d EPA and 1.2 g/d DHA), 200 mg fenofibrate or placebo treatment for 6 weeks separated by a wash-out period of at least 2-weeks. Fenofibrate changed 5 of the analysed 64 PPARalpha target genes in PBMC, 4 in muscle, and 2 in WAT, whereas fish oil changed 2 genes in WAT only. Both treatments changed 17 out of 25 similar pathways in PBMCs, related to xenobiotic metabolism, biosynthesis of steroids, lipid metabolism, transcription, proteasome function, Th1 immunity, propanoate metabolism and nucleotide metabolism. The majority (18 out of 25) of downregulated pathways in WAT were similarly changed in PBMCs after fish oil and related to lipid metabolism and amino acid metabolism. Fenofibrate and fish oil hardly affected pathways in muscle. In PBMCs, fenofibrate and fish oil only regulated 9 similar genes in metabolic syndrome-related pathways, which were IL25, TICAM1, PRDX2, PTGS1, AGK, FDPS, LDLR, TNNI3, LMAN1 and PTGS1. Overall, 6-weeks treatment with n-3 LCPUFAs and fenofibrate hardly affected PPARalpha target genes in overweight and obese subjects. Pathway analyses suggested that gene expression profiles in PBMCs can provide information about regulated metabolic processes by fish oil and fenofibrate in WAT, but not muscle. Expression of the individual genes, however, hardly overlapped between the tissues.
2025-02-01 | GSE27384 | GEO
Project description:ScopeThe drug fenofibrate and dietary fish oils can effectively lower circulating triglyceride (TG) concentrations. However, a detailed comparative analysis of the effects on the plasma metabolome is missing.Methods and resultsTwenty overweight and obese subjects participate in a double-blind, cross-over intervention trial and receive in a random order 3.7 g day-1 n-3 fatty acids, 200 mg fenofibrate, or placebo treatment for 6 weeks. Four hundred twenty plasma metabolites are measured via gas chromatography-mass spectrometry (GC-MS) and liquid chromatography-mass spectrometry (LC-MS). Among the treatments, 237 metabolites are significantly different, of which 22 metabolites change in the same direction by fish oil and fenofibrate, including a decrease in several saturated TG-species. Fenofibrate additionally changes 33 metabolites, including a decrease in total cholesterol, and total lysophosphatidylcholine (LPC), whereas 54 metabolites are changed by fish oil, including an increase in unsaturated TG-, LPC-, phosphatidylcholine-, and cholesterol ester-species. All q < 0.05.ConclusionFenofibrate and fish oil reduce several saturated TG-species markedly. These reductions have been associated with a decreased risk for developing cardiovascular disease (CVD). Interestingly, fish oil consumption increases several unsaturated lipid species, which have also been associated with a reduced CVD risk. Altogether, this points towards the power of fish oil to change the plasma lipid metabolome in a potentially beneficial way.
| S-EPMC9286410 | biostudies-literature
Project description:The effects of fenofibrate and fish oil on gene expression in peripheral blood mononuclear cells, muscle, and adipose tissue from overweight and obese individuals
| PRJNA137009 | ENA
Project description: Not available
2009-07-07 | E-MTAB-48 | biostudies-arrayexpress
Project description:Rationale: Omega-3 fatty acid (n3PUFA) supplementation has been proposed as a promising antiasthma strategy. The rs59439148 ALOX5 polymorphism affects leukotriene production and possibly inflammatory responses to n3PUFA. Objectives: Assess the effects of n3PUFA supplementation and ALOX5 genotype on asthma control in patients with obesity and uncontrolled asthma. Methods: This multicenter trial among 12- to 25-year-olds with overweight/obesity and uncontrolled asthma randomized subjects in a 3:1 allotment to n3PUFA (4 g/d) or soy oil control for 24 weeks. Asthma Control Questionnaire was the primary outcome; secondary outcomes included blood leukocyte n3PUFA levels, urinary leukotriene-E4, spirometry, and asthma-related events. The number of SP1 tandem repeats in rs59439148 determined ALOX5 genotype status. Simple and multivariable generalized linear models assessed effects on outcomes. Results: Ninety-eight participants were randomized (77 to PUFA, 21 to control), and more than 86% completed all visits. Asthma and demographic characteristics were similar among treatment groups. n3PUFA treatment increased the n3-to-n6 PUFA ratio in circulating granulocytes (P = 0.029) and monocytes (P = 0.004) but did not affect mean Asthma Control Questionnaire change at 6 months (n3PUFA: mean, -0.09; 95% confidence interval [CI], 0.09 to 0.10; vs. control: mean, -0.18; 95% CI, -0.42 to 0.06; P = 0.58). Changes in urinary leukotriene-E4 (P = 0.24), forced expiratory volume in 1 second % predicted (P = 0.88), and exacerbations (relative risk [RR], 0.92; 95% CI, 0.30-2.89) at 6 months were similar in both groups. n3PUFA treatment was associated with reduced asthma-related phone contacts (RR, 0.34; 95% CI, 0.13-0.86; P = 0.02). ALOX5 genotype did not affect n3PUFA treatment responses. Conclusions: We did not find evidence that n3PUFA use improves most asthma-related outcomes and cannot recommend it as a prevention strategy for overweight/obese patients with asthma. Clinical trial registered with www.clinicaltrials.gov (NCT01027143).
| S-EPMC6491059 | biostudies-literature
Project description:Obesity represents an important public health challenge of the twenty first century reaching epidemic proportions worldwide; this is especially true for the pediatric population. In this context, bioactive compounds from foods are crucial to counteract chronic inflammation as a typical feature of obesity. In particular, extra virgin olive oil (EVOO) is one of the most important functional foods exerting, among others, an anti-inflammatory activity not only due to its major (monounsaturated fatty acids) but also to its minor (phenolics) components, as reported in the last years. However, only a limited number of studies were performed on pediatric population, and even fewer are those focusing on EVOO phenolics that investigate the correlation of the chemical characterization with the biological function. Thus, starting from our in vitro data identifying an EVOO chemical profile characterized by a high content of secoiridoids correlating with an anti-inflammatory effect, we studied the ability of an EVOO extract with the same chemical profile to retain this function ex vivo. Specifically, peripheral blood mononuclear cells (PBMCs) collected from obese children were treated with EVOO and olive oil extracts, characterized by a low polyphenol content, to study the ability of secoiridoids to dampen the inflammatory response. A reduction of pro-inflammatory CD14+CD16+ monocytes was detected by cytofluorimetric analysis when PBMCs were treated with EVOO as compared to olive oil extracts. According to this, a down modulation of CCL2 and CCL4 chemokines involved in the recruitment of inflammatory cells, was reported in the supernatants of EVOO relative to olive oil extracts treated PBMCs. Moreover, a high-throughput gene expression analysis revealed that PBMCs molecular profile from obese children is greatly modulated after the treatment with EVOO extract in terms of metabolic and inflammatory pathways. Importantly, some of the significantly modulated genes were involved in the pathways promoting the development of severe obesity. Overall, our ex vivo data demonstrated the ability of EVOO to reduce the inflammatory milieu of PBMCs from obese children both at protein and molecular levels. Of note, a good correlation between the EVOO chemical profile and the biological modulations in terms of anti-inflammatory activity was reported.
| S-EPMC9643887 | biostudies-literature
Project description:ObjectivesTo evaluate whether a fish oil and/or probiotics intervention in pregnant women with overweight or obesity would influence the tendency of their 24-month-old children to become overweight and alter their body fat percentage.MethodsWomen (n = 439) were double-blindly randomized into 4 intervention groups: fish oil+placebo, probiotics+placebo, probiotics+fish oil, and placebo+placebo (fish oil: 1.9 g docosahexaenoic acid and 0.22 g eicosapentaenoic acid, probiotics: Lacticaseibacillus rhamnosus HN001 and Bifidobacterium animalis ssp. lactis 420, 1010 colony-forming units each). The intervention lasted from early pregnancy until 6 months postpartum. Children's (n = 330) growth data (height, weight, head circumference), a secondary outcome of the trial, were evaluated at birth, 3, 6, 12, and 24 months of age and compared to Finnish growth charts. Body fat percentage was measured with air displacement plethysmography (24 months). Logistic regression and general linear models were used to analyze the data.ResultsProbiotics+placebo [weight-for-height% adj. Odds ratio (OR) = 0.36, 95% confidence interval (CI) = 0.14-0.95] and probiotics+fish oil [weight-for-age standard deviation score (SD-score) adj. OR = 0.22, 95% CI = 0.07-0.71] associated with lower overweight odds in 24-month-old children compared to placebo+placebo. Results remained essentially the same, when probiotics' main effect (combined probiotics+placebo and probiotics+fish oil) was estimated; that is, lower overweight odds (weight-for-height% adj. OR = 0.48, 95% CI = 0.25-0.95 and weight-for-age SD-score adj. OR = 0.42, 95% CI = 0.20-0.88) compared to non-probiotics. No fish oil main effect (combined fish oil+placebo and probiotics+fish oil) was seen. The intervention did not influence body fat percentage.ConclusionsThe administration of probiotics solely and in combination with fish oil during pregnancy to women with overweight or obesity lowered the overweight odds of their 24-month-old children.
| S-EPMC9848211 | biostudies-literature
Project description:The aim of this article is to review the research into the main peripheral appetite signals altered in human obesity, together with their modifications after body weight loss with diet and exercise and after bariatric surgery, which may be relevant to strategies for obesity treatment. Body weight homeostasis involves the gut-brain axis, a complex and highly coordinated system of peripheral appetite hormones and centrally mediated neuronal regulation. The list of peripheral anorexigenic and orexigenic physiological factors in both animals and humans is intimidating and expanding, but anorexigenic glucagon-like peptide 1 (GLP-1), cholecystokinin (CCK), peptide YY (PYY) and orexigenic ghrelin from the gastrointestinal tract, pancreatic polypeptide (PP) from the pancreas and anorexigenic leptin from adiposites remain the most widely studied hormones. Homeostatic control of food intake occurs in humans, although its relative importance for eating behaviour is uncertain, compared with social and environmental influences. There are perturbations in the gut-brain axis in obese compared with lean individuals, as well as in weight-reduced obese individuals. Fasting and postprandial levels of gut hormones change when obese individuals lose weight, either with surgical or with dietary and/or exercise interventions. Diet-induced weight loss results in long-term changes in appetite gut hormones, postulated to favour increased appetite and weight regain while exercise programmes modify responses in a direction expected to enhance satiety and permit weight loss and/or maintenance. Sustained weight loss achieved by bariatric surgery may in part be mediated via favourable changes to gut hormones. Future work will be necessary to fully elucidate the role of each element of the axis, and whether modifying these signals can reduce the risk of obesity.
| S-EPMC4827002 | biostudies-literature