Search Results (5)

Background/Objectives: Metabolic dysfunction-associated steatotic liver disease (MASLD) is closely linked to Western dietary patterns. Yet, preclinical studies rely on continuous high-fat feeding, overlooking the intermittent nature of human eating. Whether dietary periodicity itself influences the gut–liver axis and MASLD pathogenesis remains unknown. We compared continuous and intermittent high-fat, high-cholesterol (HFHC) diets in guinea pigs, a model that mirrors human lipoprotein metabolism, hepatic cholesterol handling, and hindgut fermentation. Methods: Integrated multi-omics analyses (serum metabolomics, fecal 16S rRNA sequencing, and liver transcriptomics) were employed in a guinea pig model, stratified into normal diet (ND), intermittent HFHC diet (IHD), and IHD with flaxseed lignan supplementation, to compare the effects of dietary regimens and the therapeutic efficacy of lignan on hepatic pathology. Results: Both diets induced hallmark hepatic features of MASLD; however, the intermittent regimen provoked significantly more severe hepatic steatosis, inflammation, oxidative stress, and fibrosis. Hepatic transcriptomic analysis identified the PI3K-Akt signaling pathway as the most significantly enriched pathway in the IHD group. Mechanistically, this aggravated liver injury was linked to gut microbiota dysbiosis and a marked depletion of the microbial metabolite enterolactone. Fecal microbiota transplantation confirmed that the dysbiotic microbiota directly transmits the aggravated liver injury phenotype. Supplementation with flaxseed lignan, the dietary precursor of enterolactone, restored enterolactone production, corrected the dysregulated gut microbiota–enterolactone axis, and largely normalized the expression of PI3K-Akt downstream targets, thereby alleviating hepatic pathology. Conclusions: These findings suggest that alterations in the gut microbiota–enterolactone axis may contribute to diet-periodicity-driven liver injury and highlight its potential involvement in disease progression. Modulating this axis through dietary interventions, such as flaxseed lignan supplementation, may represent a promising nutritional strategy for mitigating MASLD associated with cyclical dietary exposure. Full article

Background: Inter-individual variability in lipid response to dietary interventions complicates cardiometabolic prevention in overweight and obese women. Although several dietary strategies improve lipid profiles on average, predictors of comprehensive, multi-marker lipid improvement remain unclear. Objective: To identify baseline clinical predictors of comprehensive lipid improvement across seven dietary interventions and to evaluate the performance of three machine learning (ML) classifiers in predicting a composite Global Score. Methods: This secondary analysis pooled individual-level data from 284 overweight or obese women enrolled in three randomized controlled trials (RCTs). Participants were assigned to continuous energy restriction (CER), intermittent energy restriction (IER), intermittent energy and carbohydrate restriction (IECR), IECR with added protein and fat (IECR+PF), high-carbohydrate, high-monounsaturated-fat, or daily energy-restriction diets. Eleven baseline clinical features served as predictors. Four binary lipid improvement scores (TC/HDL, LDL/HDL, non-HDL cholesterol, TG/HDL) were calculated from baseline to week 12, and a composite Global Score was defined as TRUE only when all four improved. Three ML classifiers (J48, Logistic Model Tree [LMT], Random Forest) were evaluated using stratified 10-fold cross-validation. Results: Overall, 30–35% achieved improvement in the Global Score. Improvement rates varied across diets, with High Mono and High Carb showing the highest rates (48.4%). LMT performed best (AUC = 0.66; accuracy = 70%). Baseline TG, BMI, age, total cholesterol, and weight were the strongest predictors. Conclusions: Comprehensive lipid improvement varies across dietary strategies and is influenced by baseline triglycerides, adiposity, age, and diet type. ML-based stratification may support personalized dietary prescriptions. Full article

Background/Objectives: High-altitude hypoxia may affect ECG readings, but it is unclear whether the “live-low–train-high” approach prevents these changes in winter sports athletes. Methods: This cross-sectional study assessed cardiovascular parameters in 102 winter-sport athletes (mean age 20 ± 4 y; 57% women), divided by training altitude into a high-altitude (HA) group (2500–3300 m, n = 70; skiers/snowboarders) and a low-altitude (LA) group (738 m, n = 32; ice hockey/figure skaters). Mid-season assessments included resting ECG, blood pressure, blood biochemistry, and three 24 h dietary recalls. Results: All ECG parameters were physiological, and no significant differences (p < 0.05) were observed in heart rate, PR interval, or QTc between groups. However, HA group exhibited higher systolic blood pressure and a short QT interval. Lactate was significantly higher in HA (p = 0.028). The HA diet contained more saturated fat (p < 0.001), cholesterol (p = 0.013), magnesium (p = 0.003) and potassium (p = 0.001), whereas LA athletes consumed more glucose (p = 0.024). In HA, total energy expenditure correlated positively (p ≥ 0.05) with QRS (ρ = 0.52) and QT (ρ = 0.56), while heart rate correlated inversely with vitamin D (ρ = −0.59). In LA, QTc showed strong inverse correlations with zinc (ρ = −0.62) and selenium (ρ = −0.85). Conclusions: This finding suggests that intermittent high-altitude training did not alter ECG patterns when nutrient intake was adequate. High lactate level and specific nutrient correlations point to a residual physiological load and a modulatory role of electrolytes, B-vitamins, and vitamin D on cardiac repolarisation. Full article

Obesity and overweight conditions, frequently accompanied by hypercholesterolemia, are major risk factors for cardiovascular disease. Lifestyle interventions remain the cornerstone of non-pharmacological treatment; however, their effectiveness in improving lipid profiles is limited. Intermittent hypoxic training (IHT) has recently emerged as a potential strategy to enhance metabolic outcomes. This study aimed to evaluate the effects of a 4-week intensive IHT program combined with a calorie-restricted diet on lipid profile and body composition in men with overweight or obesity and secondary hypercholesterolemia. Twenty physically inactive men (35.3 ± 5.4 years) were randomly assigned to either a hypoxic group (H, n = 10) or a normoxic control group (C, n = 10). Both groups followed the same training protocol and diet, differing only in environmental training conditions. Body composition, resting metabolic rate, and blood lipid parameters (total cholesterol, TC; high-density lipoprotein cholesterol, HDL-C; low-density lipoprotein cholesterol, LDL-C; non-high-density lipoprotein cholesterol, non-HDL-C; Triglycerides, TG) were assessed before and after the intervention. Compared with the C group, participants in the H group achieved significantly greater reductions in body mass (−5.4% vs. −2.6%, p < 0.05) and fat mass (−14.7% vs. −7%, p < 0.01). IHT also induced marked decreases in TC (−22.6%, p < 0.001), LDL-C (−25.8%, p < 0.001), non-HDL-C (−26.5%, p < 0.001), and TG (−31.4%, p < 0.01), along with a significant improvement in the atherogenic index of plasma (AIP, −24.4%, p < 0.05). In contrast, the C group showed only non-significant downward trends. No significant changes in HDL-C were observed in either group. These findings suggest that IHT combined with dietary restriction produces more favorable changes in lipid profile and body composition than normoxic training. IHT may therefore represent a promising adjunct to conventional lifestyle-based interventions in the management of obesity-related hypercholesterolemia. Full article

In humans and animal models, intermittent fasting (IF) interventions promote body weight loss, improve metabolic health, and are thought to lower cardiovascular disease risk. However, there is a paucity of reports on the relevance of such nutritional interventions in the context of dyslipidemia and atherosclerotic cardiovascular diseases. The present study assessed the metabolic and atheroprotective effects of intermittent fasting intervention (IF) in atherosclerosis-prone apolipoprotein E-deficient (Apoe^-/-) mice. Groups of male and female Apoe^-/- mice were fed a regular (chow) or atherogenic (high-fat, high-cholesterol, HFCD) diet for 4 months, either ad libitum or in an alternate-day fasting manner. The results show that IF intervention improved glucose and lipid metabolism independently of sex. However, IF only decreased body weight gain in males fed chow diet and differentially modulated adipose tissue parameters and liver steatosis in a diet composition-dependent manner. Finally, IF prevented spontaneous aortic atherosclerotic lesion formation in mice fed chow diet, irrespective of sex, but failed to reduce HFCD-diet-induced atherosclerosis. Overall, the current work indicates that IF interventions can efficiently improve glucose homeostasis and treat atherogenic dyslipidemia, but a degree of caution is warranted with regard to the individual sex and the composition of the dietary regimen. Full article