Atherosclerosis is the major contributor to cardiovascular mortality worldwide. Alternate day fasting (ADF) has gained growing attention due to its metabolic benefits. However, the effects of ADF on atherosclerotic plaque formation remain inconsistent and controversial in atherosclerotic animal models. The present study was designed to investigate the effect of ADF on atherosclerosis in apolipoprotein E-deficient (Apoe^−/−) mice. Eleven-week-old male Apoe^−/− mice fed with Western diet (WD) were randomly grouped into ad libitum (AL) group and ADF group, and ADF aggravated both the early and advanced atherosclerotic lesion formation, which might be due to the disturbed cholesterol profiles caused by ADF intervention. ADF significantly altered cholesterol metabolism pathways and down-regulated integrated stress response (ISR) in the liver. The hepatic expression of activating transcription factor 3 (ATF3) was suppressed in mice treated with ADF and hepatocyte-specific overexpression of ATF3 attenuated the effects of ADF on atherosclerotic plaque formation in Apoe^−/− mice. Moreover, the expression of ATF3 could be regulated by Krüppel-like factor 6 (KLF6) and both the expressions of ATF3 and KLF6 were regulated by hepatic cellular ISR pathway. In conclusion, ADF aggravates atherosclerosis progression in Apoe^−/− mice fed on WD. ADF inhibits the hepatic ISR signaling pathway and decreases the expression of KLF6, subsequently inhibiting ATF3 expression. The suppressed ATF3 expression in the liver mediates the deteriorated effects of ADF on atherosclerosis in Apoe^−/− mice. The findings suggest the potentially harmful effects when ADF intervention is applied to the population at high risk of atherosclerosis.

The prevalence of hypertension (HTN) is higher in patients with non-alcoholic fatty liver disease (NAFLD). Inflammation is the key link between HTN and NAFLD. Systemic inflammation can be dramatica... Patients in the highest DII tertiles group had a higher SBP and higher rates of HTN compared with patients in the lowest DII tertiles group in male participants with severe hepatic steatosis S3.DII...

Cardiac fibrosis is a cause of morbidity and mortality in people with heart disease. Anti-fibrosis treatment is a significant therapy for heart disease, bu

Background: Metabolic dysfunction–associated steatotic liver disease (MASLD) is a global health challenge, with early detection and risk stratification across glycemic states still unresolved. This study aimed to evaluate the performance of 18 non-invasive metabolic indices in predicting MASLD (defined as hepatic steatosis with metabolic risk factors) and significant fibrosis across glycemic states and demographic subgroups. Methods: Cross-sectional analyses were performed on 2,794 individuals aged ≥ 20 years from the 2017–2020 National Health and Nutrition Examination Survey cycle, stratified by glycemic status and demographic factors. Eighteen indices were assessed: triglyceride-glucose index (TyG), TyG-body mass index (TyG-BMI), TyG-waist circumference (TyG-WC), TyG-waist-to-height ratio (TyG-WHtR), TyG-weight-adjusted waist index (TyG-WWI), visceral adiposity index (VAI), homeostatic model assessment of insulin resistance (HOMA-IR), metabolic score for IR (METS-IR), Framingham steatosis index (FSI), fatty liver index (FLI), USFLI, Zhejiang University index (ZJU), lipid accumulation product (LAP), hepatic steatosis index (HSI), non-high-density lipoprotein cholesterol (HDL-C) to HDL-C ratio (NHHR), Nonalcoholic fatty liver disease fibrosis score (NFS), fibrosis-4 index (FIB-4), and BMI-aspartate aminotransferase/alanine aminotransferase ratio and diabetes score (BARD). Associations and diagnostic performance were examined using multivariable logistic regression and receiver operating characteristic analyses. Results: MASLD prevalence increased with worsening glycemic status: 40.6% in normoglycemia, 62.7% in prediabetes, and 85.5% in type 2 diabetes mellitus (T2DM). TyG-WHtR exhibited the strongest association with MASLD (odds ratio [OR] 3.83), with an even higher risk in T2DM (OR 5.58). FLI, TyG-WHtR, and NFS were associated with fibrosis, though the associations were weaker in normoglycemia. TyG-WC demonstrated the highest diagnostic accuracy for MASLD (area under the curve [AUC] 0.830), particularly in males and adults ≤ 50 years (AUCs 0.842–0.853). FLI performed consistently across glycemic strata (AUCs 0.769–0.821). FSI performed well in T2DM (AUC 0.823) and in males (AUC 0.829). For significant fibrosis, FLI showed the best performance, particularly in prediabetes (AUC 0.761) and T2DM (AUC 0.754). Traditional markers (FIB-4, BARD) demonstrated limited utility. Conclusions: Glycemic deterioration is strongly linked to MASLD and fibrosis. TyG-WC and FLI were the most consistent and high-performing indices across glycemic and demographic groups, supporting their use as broadly applicable non-invasive tools for individualized MASLD risk assessment.

Objective: To undertake a network meta-analysis to compare the relative efficacy of a dual peroxisome proliferator-activated receptor (PPAR)α and PPARγ agonist, glucagon-like peptide-1 receptor agonists (GLP-1RAs) and metformin in patients with non-alcoholic fatty liver disease (NAFLD). Methods: Electronic databases, including Embase®, PubMed® and The Cochrane Library, were searched systematically for eligible studies from inception to 20 July 2022. Randomized controlled trials (RCTs) that investigated aspartate aminotransferase, alanine aminotransferase (ALT) and triglyceride levels were considered for inclusion. Data were extracted using a standardized data collection table. A network meta-analysis was performed. Relative risk and 95% confidence interval were calculated for continuous data and I² was used to assess the heterogeneity of studies. Results: A total of 22 RCTs involving 1698 patients were eligible for inclusion in the analysis. Both direct analysis and indirect analysis showed that saroglitazar was significantly superior to GLP-1RAs in improving ALT levels. Metformin improved ALT levels, but the effect was not as good as saroglitazar. Conclusion: Saroglizatar was the most effective drug for improving NAFLD. INPLASY registration number: INPLASY202340066