Flavonoids and ω3-polyunsaturated fatty acid supplementation in renal transplant recipients: new arguments from COVID-19
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ABSTRACT:
SUBMITTER: Guida B
PROVIDER: S-EPMC8590443 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:The recent characterization of functional brown adipose tissue in adult humans has opened new perspectives for regulation of energy expenditure with respect to obesity and diabetes. Furthermore, dietary recommendations have taken into account the insufficient dietary intake of ω3 PUFAs and the concomitant excessive intake of ω6 PUFA associated with the occurrence of overweight/obesity. We aimed to study whether ω3 PUFAs could play a role in the recruitment and function of energy-dissipating brown/brite adipocytes. We show that ω3 PUFA supplementation has a beneficial effect on the thermogenic function of adipocytes. In vivo, a low dietary ω6:ω3 ratio improved the thermogenic response of brown and white adipose tissues to β3-adrenergic stimulation. This effect was recapitulated in vitro by PUFA treatment of hMADS adipocytes. We pinpointed the ω6-derived eicosanoid prostaglandin (PG)F2α as the molecular origin because the effects were mimicked with a specific PGF2α receptor agonist. PGF2α level in hMADS adipocytes was reduced in response to ω3 PUFA supplementation. The recruitment of thermogenic adipocytes is influenced by the local quantity of individual oxylipins, which is controlled by the ω6:ω3 ratio of available lipids. In human nutrition, energy homeostasis may thus benefit from the implementation of a more balanced dietary ω6:ω3 ratio.
| S-EPMC5832935 | biostudies-literature
Project description:The effect of marine-derived omega-3 polyunsaturated fatty acids (n-3 PUFA) on long-term outcome in renal transplant recipients (RTR) remains unclear. We investigated whether marine-derived n-3 PUFA intake is associated with all-cause and cardiovascular (CV) mortality in RTR. Intake of eicosapentaenoic acid plus docosahexaenoic acid (EPA-DHA) was assessed using a validated Food Frequency Questionnaire. Cox regression analyses were performed to evaluate the associations of EPA-DHA intake with all-cause and CV mortality. We included 627 RTR (age 53 ± 13 years). EPA-DHA intake was 102 (42-215) mg/day. During median follow-up of 5.4 years, 130 (21%) RTR died, with 52 (8.3%) due to CV causes. EPA-DHA intake was associated with lower risk of all-cause mortality (Hazard Ratio (HR) 0.85; 95% confidence interval (95% CI) 0.75-0.97). Age (p= 0.03) and smoking status (p = 0.01) significantly modified this association, with lower risk of all-cause and CV mortality particularly in older (HR 0.75, 95% CI 0.61-0.92; HR 0.68, 95% CI 0.48-0.95) and non-smoking RTR (HR 0.80, 95% CI 0.68-0.93; HR 0.74, 95% CI 0.56-0.98). In conclusion, marine-derived n-3 PUFA intake is inversely associated with risk of all-cause and CV mortality in RTR. The strongest associations were present in subgroups of patients, which adds further evidence to the plea for EPA-DHA supplementation, particularly in elderly and non-smoking RTR.
| S-EPMC5409702 | biostudies-literature
Project description:Mycophenolic acid (MPA), an immunosuppressive drug widely used in kidney transplantation, has been suggested to have anti-fibrotic effects. To analyze at a genomic level these effects, we prospectively studied a group of stable kidney transplant recipients (n=35) on cyclosporine (CyA) and azathioprine treatment. Twenty patients were converted from azathioprine to MPA (MPA group) and 15 patients continued on azathioprine (AZA group). RNA was extracted by peripheral blood mononuclear cells at baseline and 3 months thereafter. Genomic analysis, performed on 5 randomly-selected MPA patients, revealed that 17 genes discriminated the transcriptomic profile after conversion. Neutral endopeptidase (NEP), an enzyme degrading angiotensin-II, was the most significant up-regulated gene. NEP expression level was inversely correlated to proteinuria at baseline and after conversion. Immunohistochemistry on graft biopsy of 33 independent patients demonstrated higher glomerular and tubular NEP protein expression in CyA+MPA (n=13) compared to CyA+AZA (n=12) and CyA alone (n=8). Glomerular NEP levels were inversely correlated to proteinuria and glomerulosclerosis. Tubular NEP expression was inversely correlated to interstitial fibrosis. Incubation of proximal tubular cells with MPA led to a dose- and time-dependent increase of NEP gene expression. The direct influence of MPA on NEP expression may suggest a novel therapeutic effect of this drug.
2010-12-22 | GSE14630 | GEO
Project description:Mycophenolic acid (MPA), an immunosuppressive drug widely used in kidney transplantation, has been suggested to have anti-fibrotic effects. To analyze at a genomic level these effects, we prospectively studied a group of stable kidney transplant recipients (n=35) on cyclosporine (CyA) and azathioprine treatment. Twenty patients were converted from azathioprine to MPA (MPA group) and 15 patients continued on azathioprine (AZA group). RNA was extracted by peripheral blood mononuclear cells at baseline and 3 months thereafter. Genomic analysis, performed on 5 randomly-selected MPA patients, revealed that 17 genes discriminated the transcriptomic profile after conversion. Neutral endopeptidase (NEP), an enzyme degrading angiotensin-II, was the most significant up-regulated gene. NEP expression level was inversely correlated to proteinuria at baseline and after conversion. Immunohistochemistry on graft biopsy of 33 independent patients demonstrated higher glomerular and tubular NEP protein expression in CyA+MPA (n=13) compared to CyA+AZA (n=12) and CyA alone (n=8). Glomerular NEP levels were inversely correlated to proteinuria and glomerulosclerosis. Tubular NEP expression was inversely correlated to interstitial fibrosis. Incubation of proximal tubular cells with MPA led to a dose- and time-dependent increase of NEP gene expression. The direct influence of MPA on NEP expression may suggest a novel therapeutic effect of this drug. For microarray analysis, we studied 5 randomly selected patients included in the training group. Patients included in this group were, at the time of enrollment (T0), on standard maintenance immunosuppression with Cyclosporine (Neoral, Novartis, Basel, mean±SD of daily dose: 160.1±37.1mg), prednisone (5 mg daily) and Azathioprine (50 mg daily). Twenty patients, at T0, were switched from Azathioprine to EC-MPS (Myfortic, Novartis, Basel, 720 mg bid) for their need of allopurinol therapy (EC-MPS group). However, to avoid confounding factors, allopurinol treatment did not start until the end of our study (3 months). For the microarray analysis, we randomly selected 5 patients from the EC-MPS group. PBMC both at T0 and at T1 (3 months after the switching of the therapy) were immediately isolated from 20 ml of whole blood by Ficoll–Hypaque (Flow Laboratories, Irvine, UK) density gradient centrifugation. Total RNA was extracted by RNeasy mini kit (QIAGEN Inc., Valencia, CA) according the manufacturer’s instructions. Total RNA was processed and hybridized to the Affymetrix GeneChips Human Genome U133 Array Set HG-U133A (Affymetrix)(Affymetrix, Santa Clara, CA)
2010-12-22 | E-GEOD-14630 | biostudies-arrayexpress
Project description: Not available
| S-DIXA-D-1025 | biostudies-other
Project description:ObjectiveAn increased ω6/ω3-polyunsaturated fatty acid ratio in the current Western diet is regarded as a critical epigenetic nutritional factor in the pathogenesis of several human lifestyle diseases, metabolic syndrome, cardiovascular disease, the central nervous system and the female and male reproductive systems. The impact of nutrient ω3-and ω6-PUFAs in the pathogenesis of dyslipoproteinemia and atherosclerosis has been a topic of intense efforts for several decades. Cellular homeostasis of the ω3-and ω6- PUFA pool is maintained by the synthesis of ω3-and ω6-PUFAs from essential fatty acids (EFA) (linoleic and α-linolenic acid) and their dietary supply. In this study, we used the auxotrophic Δ6-fatty acid desaturase- (FADS2) deficient mouse (fads2-/-), an unbiased model congenial for stringent feeding experiments, to investigate the molecular basis of the proposed protective role of dietary ω3-and ω6-PUFAs (Western diet) in the pathogenesis of multifactorial dyslipoproteinemia and atherosclerosis. We focused on the metabolic axis-liver endoplasmic reticulum (ER), serum lipoprotein system (Lp) and aorta vessel wall. Furthermore, we addressed the impact of the inactivated fads2-locus with inactivated PUFA synthesis on the development and progression of extended atherosclerosis in two different mouse mutants with disrupted cholesterol homeostasis, using the apoe-/- and ldlr-/- mutants and the fads2-/- x apoe-/- and fads2-/- x ldlr-/- double mutants.MethodsCohorts of +/+ and fads2-/- mice underwent two long-term dietary regimens: a) a PUFA-free standard chow diet containing only EFAs, essential for viability, and b) a high fat/high cholesterol (HFHC) diet, a mimicry of the human atherogenic "Western" diet. c) To study the molecular impact of PUFA synthesis deficiency on the development and progression of atherosclerosis in the hypercholesterolemic apoe-/- and ldlr-/- mouse models fed PUFA-free regular and sustained HFHC diets, we generated the fads2-/- x apoe-/- and the fads2-/- x ldlr-/- double knockout mutants. We assessed essential molecular, biochemical and cell biological links between the diet-induced modified lipidomes of the membrane systems of the endoplasmic reticulum/Golgi complex, the site of lipid synthesis, the PL monolayer and neutral lipid core of LD and serum-Lp profiles and cellular reactions in the aortic wall.Resultsω3-and ω6-PUFA synthesis deficiency in the fads2-/- mouse causes a) hypocholesterolemia and hypotriglyceridemia, b) dyslipoproteinemia with a shift of high-density lipoprotein (HDL) to very low-density lipoprotein (VLDL)-enriched Lp-pattern and c) altered liver lipid droplet structures. d) Long-term HFHC diet does not trigger atherosclerotic plaque formation in the aortic arc, the thoracic and abdominal aorta of PUFA-deficient fads2-/- mice. Inactivation of the fads2-/- locus, abolishing systemic PUFA synthesis in the fads2-/- x apoe-/- and fads2-/- x ldlr-/- double knockout mouse lines.ConclusionsDeficiency of ω3-and ω6-PUFA in the fads2-/- mutant perturbs liver lipid metabolism, causes hypocholesterolemia and hypotriglyceridemia and renders the fads2-/- mutant resistant to sustained atherogenic HFHC diet. Neither PUFA-free regular nor long-term HFHC-diet impacts the apoe- and LDL-receptor deficiency-provoked hypercholesterolemia and atherosclerotic plaque formation, size and distribution in the aorta. Our study strongly suggests that the absence of PUFAs as highly vulnerable chemical targets of autoxidation attenuates inflammatory responses and the formation of atherosclerotic lesions. The cumulative data and insight into the molecular basis of the pleiotropic functions of PUFAs challenge a differentiated view of PUFAs as culprits or benefactors during a lifespan, pivotal for legitimate dietary recommendations.
| S-EPMC8479258 | biostudies-literature
Project description: Not available
| S-EPMC6464137 | biostudies-literature
Project description: Not available
| S-EPMC6464574 | biostudies-literature
Project description:Background and objectivesAcidosis is prevalent among renal transplant recipients (RTRs) and adversely affects cardiometabolic processes. Factors contributing to acidosis are graft dysfunction and immunosuppressive drugs. Little is known about the potential influence of diet on acidosis in RTRs. This study examined the association of metabolic acid load with acidosis and with cardiovascular risk factors in RTRs and aimed to identify dietary factors associated with acidosis. DESIGN, PARTICIPANTS, SETTING, & MEASUREMENTS: 707 RTRs were included. Metabolic acid load was assessed by measuring 24-hour urinary net acid excretion (NAE; i.e., titratable acid + ammonium - bicarbonate). Acidosis was defined as serum [HCO(3)(-)] < 24 mmol/L. BP and insulin resistance, reflected by hemoglobin A1c, were among cardiovascular risk factors. Diet was assessed with food-frequency questionnaires. Linear regression analysis was applied to investigate association between NAE and acidosis and between dietary factors and acidosis.ResultsMean age ± SD was 53 ± 13 years; 57% of patients were male. Acidosis was present in 31% of RTRs. NAE was associated with acidosis (serum HCO(3)(-): β=-0.61; serum pH: β=-0.010; both P<0.001). Patients with high intake of animal protein (i.e., from meat, cheese, and fish) and low intake of fruits and vegetables had significantly lower serum HCO(3)(-) and serum pH. No associations were observed between NAE and cardiovascular risk factors, such as hypertension and insulin resistance.ConclusionsIn addition to conventional factors contributing to acidosis, diet might influence acid-base homeostasis in RTRs. Higher intake of fruits and vegetables and lower animal protein intake is associated with less acidosis in RTRs.
| S-EPMC3488949 | biostudies-literature
Project description:Rationale & objectiveDeterioration of kidney graft function is associated with accelerated cellular senescence. Marine n-3 polyunsaturated fatty acids (PUFAs) have favorable properties that may counteract cellular senescence development and damage caused by the senescence-associated secretory phenotype (SASP) secretome. Our objective was to investigate the potential effects of marine n-3 PUFA supplementation on the SASP secretome in kidney transplant recipients.Study designExploratory substudy of the Omega-3 Fatty Acids in Renal Transplantation trial.Setting & participantsAdult kidney transplant recipients with a functional kidney graft (defined as having an estimated glomerular filtration rate of >30 mL/min/1.73 m2) 8 weeks after engraftment were included in this study conducted in Norway.Analytical approachThe intervention consisted of 2.6 g of a marine n-3 PUFA or olive oil (placebo) daily for 44 weeks. The outcome was a predefined panel of SASP components in the plasma and urine.ResultsA total of 132 patients were enrolled in the Omega-3 Fatty Acids in Renal Transplantation trial, and 66 patients were allocated to receive either the study drug or placebo. The intervention with the marine n-3 PUFA was associated with reduced plasma levels of granulocyte colony-stimulating factor, interleukin 1α, macrophage inflammatory protein 1α, matrix metalloproteinase (MMP)-1, and MMP-13 compared with the intervention in the control group.LimitationsPost hoc analysis.ConclusionsThe results suggest that marine n-3 PUFA supplementation has mitigating effects on the plasma SASP components granulocyte colony-stimulating factor, interleukin 1α, macrophage inflammatory protein 1α, MMP-1, and MMP-13 in kidney transplant recipients. Future studies with kidney transplant recipients in maintenance phase, combined with an evaluation of cellular senescence markers in kidney transplant biopsies, are needed to further elucidate the potential antisenescent effect of marine n-3 PUFAs. This trial is registered as NCT01744067.
| S-EPMC8664741 | biostudies-literature