Light pollution disturbs circadian rhythm, and this can also be deleterious to the heart by increased susceptibility to arrhythmias. Herein, we investigated if rats exposed to continuous light had altered myocardial gene transcripts and/or protein expression which affects arrhythmogenesis. We then assessed if Omacor® supplementation benefitted affected rats. Male and female spontaneously hypertensive (SHR) and normotensive Wistar rats (WR) were housed under standard 12 h/12 h light/dark cycles or exposed to 6-weeks continuous 300 lux light for 24 h. Half the rats were then treated with 200 mg/100 g b.w. Omacor®. Continuous light resulted in higher male rat vulnerability to malignant ventricular fibrillation (VF). This was linked with myocardial connexin-43 (Cx43) down-regulation and deteriorated intercellular electrical coupling, due in part to increased pro-inflammatory NF-κB and iNOS transcripts and decreased sarcoplasmic reticulum Ca2+ATPase transcripts. Omacor® treatment increased the electrical threshold to induce the VF linked with amelioration of myocardial Cx43 mRNA and Cx43 protein levels and the suppression of NF-κB and iNOS. This indicates that rat exposure to continuous light results in deleterious cardiac alterations jeopardizing intercellular Cx43 channel-mediated electrical communication, thereby increasing the risk of malignant arrhythmias. The adverse effects were attenuated by treatment with Omacor®, thus supporting its potential benefit and the relevance of monitoring omega-3 index in human populations at risk.
- Klíčová slova
- NF-κB, cardiac arrhythmias, connexin-43, iNOS, light pollution, omacor, rats,
- MeSH
- fixní kombinace léků MeSH
- fyziologický stres * MeSH
- hypertenze komplikace MeSH
- konexin 43 metabolismus MeSH
- krevní tlak účinky léků MeSH
- krysa rodu Rattus MeSH
- kyselina eikosapentaenová aplikace a dávkování chemie farmakologie MeSH
- kyseliny dokosahexaenové aplikace a dávkování chemie farmakologie MeSH
- modely nemocí na zvířatech MeSH
- potkani inbrední SHR MeSH
- potkani Wistar MeSH
- potravní doplňky * MeSH
- srdce účinky léků MeSH
- srdeční arytmie komplikace patofyziologie prevence a kontrola MeSH
- světelné znečištění * MeSH
- vodní organismy MeSH
- zvířata MeSH
- Check Tag
- krysa rodu Rattus MeSH
- mužské pohlaví MeSH
- ženské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- Názvy látek
- fixní kombinace léků MeSH
- konexin 43 MeSH
- kyselina eikosapentaenová MeSH
- kyseliny dokosahexaenové MeSH
- Omacor MeSH Prohlížeč
Obesity is believed to be associated with a dysregulated endocannabinoid system which may reflect enhanced inflammation. However, reports of this in human white adipose tissue (WAT) are limited and inconclusive. Marine long-chain omega-3 polyunsaturated fatty acids (LC n-3 PUFAs) have anti-inflammatory actions and therefore may improve obesity-associated adipose tissue inflammation. Therefore, fatty acid (FA) concentrations, endocannabinoid concentrations, and gene expression were assessed in subcutaneous WAT (scWAT) biopsies from healthy normal weight individuals (BMI 18.5-25 kg/m2) and individuals living with metabolically healthy obesity (BMI 30-40 kg/m2) prior to and following a 12-week intervention with 3 g fish oil/day (1.1 g eicosapentaenoic acid (EPA) + 0.8 g DHA) or 3 g corn oil/day (placebo). WAT from individuals living with metabolically healthy obesity had higher n-6 PUFAs and EPA, higher concentrations of two endocannabinoids (anandamide (AEA) and eicosapentaenoyl ethanolamide (EPEA)), higher expression of phospholipase A2 Group IID (PLA2G2D) and phospholipase A2 Group IVA (PLA2G4A), and lower expression of CNR1. In response to fish oil intervention, WAT EPA increased to a similar extent in both BMI groups, and WAT DHA increased by a greater extent in normal weight individuals. WAT EPEA and docosahexaenoyl ethanolamide (DHEA) increased in normal weight individuals only and WAT 2-arachidonyl glycerol (2-AG) decreased in individuals living with metabolically healthy obesity only. Altered WAT fatty acid, endocannabinoid, and gene expression profiles in metabolically healthy obesity at baseline may be linked. WAT incorporates n-3 PUFAs when their intake is increased which affects the endocannabinoid system; however, effects appear greater in normal weight individuals than in those living with metabolically healthy obesity.
- Klíčová slova
- LC n-3 PUFA, adipose tissue, endocannabinoids, lipids, obesity,
- MeSH
- časové faktory MeSH
- dospělí MeSH
- dvojitá slepá metoda MeSH
- endokanabinoidy metabolismus MeSH
- fixní kombinace léků MeSH
- fosfolipasy A2, skupina II metabolismus MeSH
- fosfolipasy A2, skupina IV metabolismus MeSH
- kyselina eikosapentaenová aplikace a dávkování MeSH
- kyseliny arachidonové metabolismus MeSH
- kyseliny dokosahexaenové aplikace a dávkování MeSH
- lidé středního věku MeSH
- lidé MeSH
- metabolicky zdravá obezita diagnóza farmakoterapie metabolismus MeSH
- mladiství MeSH
- mladý dospělý MeSH
- podkožní tuk účinky léků metabolismus MeSH
- polynenasycené alkamidy metabolismus MeSH
- potravní doplňky * MeSH
- receptor kanabinoidní CB1 metabolismus MeSH
- výsledek terapie MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mladiství MeSH
- mladý dospělý MeSH
- mužské pohlaví MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- randomizované kontrolované studie MeSH
- Geografické názvy
- Anglie MeSH
- Názvy látek
- anandamide MeSH Prohlížeč
- CNR1 protein, human MeSH Prohlížeč
- endokanabinoidy MeSH
- fixní kombinace léků MeSH
- fosfolipasy A2, skupina II MeSH
- fosfolipasy A2, skupina IV MeSH
- kyselina eikosapentaenová MeSH
- kyseliny arachidonové MeSH
- kyseliny dokosahexaenové MeSH
- N-docosahexaenoylethanolamide MeSH Prohlížeč
- PLA2G2D protein, human MeSH Prohlížeč
- PLA2G4A protein, human MeSH Prohlížeč
- polynenasycené alkamidy MeSH
- receptor kanabinoidní CB1 MeSH
AIMS/HYPOTHESIS: Diets rich in n-3 polyunsaturated fatty acids, namely eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), protect against insulin resistance and obesity in rodents and increase insulin sensitivity in healthy humans. We tested whether the anti-diabetic effects of EPA and DHA involve enhanced production of the endogenous insulin sensitiser, adiponectin. METHODS: We studied the effects, in an obesity-promoting high-fat diet, of partial replacement of vegetable oils by EPA/DHA concentrate (6% EPA, 51% DHA) over a 5-week period in adult male C57BL/6J mice that either had free access to food or had their food intake restricted by 30%. At the end of the treatment, systemic markers of lipid and glucose metabolism and full-length adiponectin and leptin were measured. Adiponectin (Adipoq) and leptin (Lep) gene expression in dorsolumbar and epididymal white adipose tissue (WAT) and isolated adipocytes was quantified and adipokine production from WAT explants evaluated. RESULTS: In mice with free access to food, plasma triacylglycerols, NEFA, and insulin levels were lower in the presence of EPA/DHA, while glucose and leptin levels were not significantly altered. Food restriction decreased plasma triacylglycerols, glucose, insulin and leptin, but not adiponectin. EPA/DHA increased plasma adiponectin levels, independent of food intake, reflecting the stimulation of Adipoq expression in adipocytes and the release of adiponectin from WAT, particularly from epididymal fat. Expression of Lep and the release of leptin from WAT, while being extremely sensitive to caloric restriction, was unaltered by EPA/DHA. CONCLUSIONS/INTERPRETATION: Intake of diets rich in EPA and DHA leads to elevated systemic concentrations of adiponectin, largely independent of food intake or adiposity and explain, to some extent, their anti-diabetic effects.
- MeSH
- adiponektin biosyntéza krev genetika MeSH
- aktivace enzymů MeSH
- dietní tuky aplikace a dávkování farmakologie MeSH
- glukosa metabolismus MeSH
- inzulin krev fyziologie MeSH
- inzulinová rezistence MeSH
- kalorická restrikce MeSH
- kinasy AMP aktivovaných proteinkinas MeSH
- kyselina eikosapentaenová aplikace a dávkování farmakologie MeSH
- kyseliny dokosahexaenové aplikace a dávkování farmakologie MeSH
- leptin analýza krev genetika fyziologie MeSH
- myši inbrední C57BL MeSH
- myši MeSH
- obezita patofyziologie prevence a kontrola MeSH
- polymerázová řetězová reakce s reverzní transkripcí MeSH
- přijímání potravy MeSH
- proteinkinasy metabolismus MeSH
- regulace genové exprese MeSH
- složení těla MeSH
- triglyceridy krev MeSH
- tuková tkáň chemie metabolismus MeSH
- tukové buňky chemie metabolismus MeSH
- zvířata MeSH
- Check Tag
- mužské pohlaví MeSH
- myši MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Názvy látek
- adiponektin MeSH
- dietní tuky MeSH
- glukosa MeSH
- inzulin MeSH
- kinasy AMP aktivovaných proteinkinas MeSH
- kyselina eikosapentaenová MeSH
- kyseliny dokosahexaenové MeSH
- leptin MeSH
- proteinkinasy MeSH
- triglyceridy MeSH