Resveratrol on the Metabolic Reprogramming in Liver: Implications for Advanced Atherosclerosis

Abstract

Background/Aims: Atherosclerosis (AS) is one of the major leading causes of death globally, which is highly correlated with metabolic abnormalities. Resveratrol (REV) exerts beneficial effects on atherosclerosis. Our aim is to clarify the involvement of liver metabolic reprogramming and the atheroprotective effects of REV.Methods: ApoE-deficient mice were administered with normal diet (N), high-fat diet (H), or HFD with REV (HR). Twenty-four weeks after treatment, Oil Red O staining was used to assess the severity of AS. Non-targeted metabolomics was employed to obtain metabolic signatures of the liver from different groups.Results: High-fat diet–induced AS was alleviated by REV, with less lipid accumulation in the lesions. The metabolic profiles of liver tissues from N, H, and HR groups were analyzed. A total of 1,146 and 765 differentially expressed features were identified between N and H groups, and H and HR groups, respectively. KEGG enrichment analysis uncovered several metabolism-related pathways, which are potential pathogenesis mechanisms and therapeutic targets including “primary bile acid biosynthesis,” “phenylalanine metabolism,” and “glycerophospholipid metabolism.” We further conducted trend analysis using 555 metabolites with one-way ANOVA, where p < 0.05 and PLS-DA VIP >1. We found that REV could reverse the detrimental effect of high-fat diet–induced atherosclerosis. These metabolites were enriched in pathways including “biosynthesis of unsaturated fatty acids” and “intestinal immune network for IgA production.” The metabolites involved in these pathways could be the potential biomarkers for AS-related liver metabolic reprogramming and the mechanism of REV treatment.Conclusions: REV exerted atheroprotective effects partially by modulating the liver metabolism.

KLF7 Alleviates Atherosclerotic Lesions and Inhibits Glucose Metabolic Reprogramming in Macrophages by Regulating HDAC4/miR-148b-3p/NCOR1

“…AS is closely linked with system metabolic abnormity [39, 40]. To confirm the impact of KLF7 on the metabolism of AS mice, we detected metabolic indexes of HFD mice.…”

“…Similarly, recruitment of KLF4 reduces the AS lesion area and delays the AS development [47, 48]. In addition, AS plaque pathogenesis is also associated with system metabolic abnormality [39, 40]. Therefore, we explored the impact of KLF7 on lipid and glucose metabolism in AS, and our subsequent experiments revealed that KLF7 overexpression increased HDL-C and decreased TC, TG, LDL-C, FPG, and glucose tolerance.…”

Proteotoxic stress response in atherosclerotic cardiovascular disease: Emerging role of heat shock factor 1

“…Despite advancements in the study of atherosclerosis, the field lacks a systemic understanding of mechanisms of the disease, particularly in molecular regulators with significant pathophysiological commonalities between intracellular proteome homeostasis and atherosclerosis. Growing evidence supports the concept that aberrations in the metabolic programming contribute to the development of atherosclerosis (16,17). Chronic inflammation induced by metabolic perturbance is also associated with disordered proteomic stability in atherosclerosis (18).…”

5-ASA can functionally replace Clostridia to prevent a post-antibiotic bloom ofCandida albicansby maintaining epithelial hypoxia

“…However, as the population greatest at risk of invasive candidiasis are those with hematologic malignancies, this strategy raises safety concerns. While probiotics can act as PPAR-γ agonists (Hasan, Rahman et al 2019) and reduce Candida colonization (Archambault and Dongari-Bagtzoglou 2022), probiotics or full fecal microbiota transplants are not typically considered in hematologic malignancy due to safety concerns over infections stemming from the deleterious effects of chemotherapy (Ma, Li et al 2021). Additionally, in patients on antibiotic prophylaxis, probiotics or fecal microbiota transplants are not likely to engraft successfully.…”