Sex-Dependent Effects of Eicosapentaenoic Acid on Hepatic Steatosis in UCP1 Knockout Mice

Visceral obesity may be a driving factor in nonalcoholic fatty liver disease (NAFLD) development. Previous studies have shown that the omega-3 polyunsaturated fatty acid, eicosapentaenoic acid (EPA), ameliorates obesity in high-fat (HF) fed male, C57Bl/6 mice at thermoneutral conditions, independent of uncoupling protein 1 (UCP1). Our goals herein were to investigate sex-dependent mechanisms of EPA in the livers of wild type (WT) and UCP1 knockout (KO) male and female mice fed a HF diet (45% kcal fat; WT-HF, KO-HF) with or without supplementation of 36 g/kg EPA (WT-EPA, KO-EPA). KO significantly increased body weight in males, with no significant reductions with EPA in the WT or KO groups. In females, there were no significant differences in body weight among KO groups and no effects of EPA. In males, liver TGs were significantly higher in the KO-HF group and reduced with EPA, which was not observed in females. Accordingly, gene and protein markers of mitochondrial oxidation, peroxisomal biogenesis and oxidation, as well as metabolic futile cycles were sex-dependently impacted by KO and EPA supplementation. These findings suggest a genotypic difference in response to dietary EPA supplementation on the livers of male and female mice with diet-induced obesity and housed at thermoneutrality

The effects of yoga and quiet rest on subjective levels of anxiety and physiological correlates: a 2-way crossover randomized trial

Abstract Background Rest or acute exercise can decrease state anxiety, with some evidence showing exercise to prevent laboratory-induced elevations in anxiety. No study has examined whether yoga provides short-term protection against laboratory-induced anxiety. The aim of this study was to examine the effectiveness of an acute YogaFit session on state anxiety and measures of heart rate variability (HRV) to determine whether yoga provides short-term protection against emotional picture stimuli. Methods A randomized repeated-measures crossover clinical trial was performed. Forty healthy, female college students completed a 30 min session of YogaFit and a time-matched seated rest condition on separate days. After each condition, participants viewed 30 min of emotional picture stimuli. State anxiety, heart rate and time-domain and frequency-domain measures of HRV were assessed baseline, post- condition, and post-exposure to emotional stimuli. Data were analysed using a condition x time (2 × 3) repeated-measures ANOVA. Results Post-hoc comparisons indicate the following: (1) state anxiety significantly decreased from baseline to post-condition for both yoga and rest (p = 0.001) but returned to baseline values following exposure to emotional stimuli (p < 0.001) for both conditions; (2) heart rate decreased post-condition to post-exposure (p = 0.020) and baseline to post-exposure (p = 0.033) for both conditions; (3) time-domain measure of HRV showed a significant increase in HRV between baseline and post-condition (p = 0 .019), post-condition and post-exposure (p = 0 .007), and between baseline and post-exposure (p < 0.001). Conclusions Both YogaFit and seated rest were effective at acutely reducing state anxiety post-condition, but not at preventing an induced anxiety response post-exposure. Following exposure to the emotionally stimulating pictures, there was a shift from the high frequency-domain to the low frequency-domain and an increase in the time-domain measure of HRV for both the YogaFit and the quiet rest condition. Trial registration Retrospectively registered 2/16/2018, clinicaltrials.gov, Identifier: NCT03458702

Eicosapentaenoic Acid Improves Hepatic Metabolism and Reduces Inflammation Independent of Obesity in High-Fat-Fed Mice and in HepG2 Cells

The prevalence of nonalcoholic fatty liver disease (NAFLD) is increasing worldwide, concurrent with increased obesity. Thus, there is urgent need for research that can lead to effective NAFLD prevention/treatment strategies. Omega-3 polyunsaturated fatty acids (n-3 PUFAs), including eicosapentaenoic acid (EPA), improve inflammation- and dyslipidemia-related metabolic disorders; however, mechanisms mediating the benefits of n-3 PUFAs in NAFLD treatment are less understood. We previously reported that EPA reversed obesity-induced hepatic steatosis in high-fat (HF)-fed B6 mice. Utilizing a combination of biochemical analyses of liver tissues from HF and HF-EPA-fed mice and a series of in vitro studies in tumor necrosis factor-alpha (TNF-&alpha;)-stimulated HepG2 cells, we dissect the mechanistic effects of EPA in reducing hepatic steatosis, including the role of EPA-targeted microRNAs (miRNA). With EPA, hepatic lipid metabolism was improved in HF-EPA mice, as indicated by decreased protein and messenger RNA (mRNA) levels of fatty acid synthase (FASN) and acetyl-CoA carboxylase (Acaca) gene, and increased mRNA levels for the peroxisome proliferator activated receptor-&alpha; (Ppar&alpha;), and carnitine palmitoyltransferase (Cpt) 1a and 2 genes in the HF-EPA mice. Additionally, inflammation was reduced, as shown by decreased tumor necrosis factor-alpha (Tnf&alpha;) gene expression. Accordingly, EPA also significantly reduced FASN and ACACA mRNAs in human HepG2 cells. Glycolysis, estimated by extracellular acidification rate, was significantly reduced in HepG2 cells treated with EPA vs. vehicle. Furthermore, we identified several miRNAs that are regulated by EPA in mouse liver, including miR-19b-3p, miR-21a-5p, and others, which target lipid metabolism and inflammatory pathways. In conclusion, our findings provide novel mechanistic evidence for beneficial effects of EPA in NAFLD, through the identification of specific genes and miRNAs, which may be further exploited as future NAFLD therapies