Fat-1 ameliorates MAFLD and atherosclerosis through promoting the nuclear localization of PPARα in hamsters DOI Creative Commons
Wenxi Zhang, Jiabao Guo,

Guolin Miao

et al.

Research, Journal Year: 2024, Volume and Issue: 8

Published: Dec. 21, 2024

Fat-1, an enzyme encoded by the fat-1 gene, is responsible for conversion of endogenous omega-6 polyunsaturated fatty acids into omega-3 in Caenorhabditis elegans. To better investigate whether expression Fat-1 will exert a beneficial function dyslipidemia and metabolic dysfunction-associated liver disease (MAFLD), we established adeno-associated virus 9 expressing Fat-1. We found that adeno-associated-virus-mediated markedly reduced levels plasma triglycerides total cholesterol but increased high-density lipoprotein male wild-type hamsters on both chow diet high-fat as well chow-diet-fed LDLR-/- hamsters. ameliorated diet-induced MAFLD enhancing acid oxidation through hepatic peroxisome proliferator-activated receptor α (PPARα)-dependent pathway. Mechanistically, multiple lipid derivatives ligands PPARα simultaneously facilitated nuclear localization PPARα. Our results provide new insights therapeutic potentials to treat dyslipidemia, MAFLD, atherosclerosis.

Language: Английский

Prioritization of lipid metabolism targets for the diagnosis and treatment of cardiovascular diseases DOI Creative Commons
Zhihua Wang, Shuo Chen, Fanshun Zhang

et al.

Research, Journal Year: 2025, Volume and Issue: 8

Published: Jan. 1, 2025

Background: Cardiovascular diseases (CVD) are a major global health issue strongly associated with altered lipid metabolism. However, metabolism-related pharmacological targets remain limited, leaving the therapeutic challenge of residual lipid-associated cardiovascular risk. The purpose this study is to identify potentially novel genes by systematic genomic and phenomics analysis, an aim discovering new diagnosis biomarkers for CVD. Methods: In study, we conducted comprehensive multidimensional evaluation 881 genes. Using genome-wide association (GWAS)-based mendelian randomization (MR) causal inference methods, screened causally linked occurrence development Further validation was performed through colocalization analysis in 2 independent cohorts. Then, employed reverse screening using phenonome-wide studies (PheWAS) drug target–drug analysis. Finally, integrated serum proteomic data develop machine learning model comprising 5 proteins disease prediction. Results: Our initial yielded 54 Colocalization cohorts prioritized 29 marked correlated Comparison interaction identified 13 potential treating CVD its complications. A incorporating prediction achieved high accuracy 96.1%, suggesting as diagnostic tool clinical practice. Conclusion: This comprehensively reveals complex relationship between metabolism regulatory findings provide insights into pathogenesis drugs treatment. Additionally, developed offers promising CVD, paving way future research applications.

Language: Английский

Citations

1
Lactobacillus fermentum 166, Derived from Yak Yogurt from Tibetan Areas of Sichuan, Improves High-Fat-Diet-Induced Hyperlipidemia by Modulating Gut Microbiota and Liver- and Gut-Related Pathways DOI Creative Commons
Shiqi Zhang, Limei Xu, Chenglin Zhu

et al.

Foods, Journal Year: 2025, Volume and Issue: 14(5), P. 867 - 867

Published: March 3, 2025

The consumption of an unbalanced diet, such as a high-fat is strongly associated with hyperlipidemia and significantly contributes to the development cardiovascular cerebrovascular diseases, which are leading causes death worldwide. Globally, about 17.9 million people die disease each year (WHO 2023). Probiotics have emerged promising intervention alleviate hyperlipidemia. Therefore, this study investigates effects Lactobacillus fermentum 166 (LF-166), isolated from yak yogurt in Sichuan Tibetan area, on lipid metabolism liver gut microbiota high-fat-diet-induced hyperlipidemic mice. results revealed that (LF-166) treatment reduced body weight decreased blood levels these Based histopathological findings, LF-166 could steatosis colon injury. Additionally, 16S rRNA sequencing mice's colonic contents showed Firmicutes/Bacteroidetes (F/B) value enhanced richness diversity microbiota. regulated hepatic through up-regulation genes Lxr, Ampkα, Fxr, Hsl, Atgl down-regulation C/ebpα Pparγ liver; it also intestinal by up-regulating Abcg5 Abcg8 ileum down-regulating expression Npc1l1, Asbt, Ibabp. Thus, may inhibit progression modulating key involved metabolism, influencing liver-gut axis, regulating systemic metabolism.

Language: Английский

Citations

0
Multi-omics analysis of Au@Pt nanozyme for the modulation of glucose and lipid metabolism DOI Creative Commons
Yanan Wang, Qi Zhang,

Minrui Kan

et al.

Journal of Nanobiotechnology, Journal Year: 2024, Volume and Issue: 22(1)

Published: Aug. 31, 2024

Au@Pt nanozyme, a bimetallic core–shell structure Au and Pt nanoparticle, has attracted significant attention due to its excellent catalytic activity stability. Here, we propose that improves glucose tolerance reduces TG after four weeks administration. The transcriptomic analysis of mouse liver tissues treated with nanozyme showed changes in genes related lipid metabolism signaling pathways, including glycolysis/gluconeogenesis, pyruvate metabolism, PPAR signaling, insulin signaling. Moreover, fecal samples from mice the abundance beneficial gut microbiota such as Dubosiella, Parvibacter, Enterorhabdus, Monoglobus, Lachnospiraceae_UCG-008, Lachnospiraceae_UCG-006, Lachnospiraceae_UCG-001, Christensenellaceae_R-7_group. Combined multi-omics correlation analyses revealed modulation by was strongly correlated hepatic gene expression profiles well microbial profiles. Overall, our integrated demonstrated could modulate regulating key altering composition microbiota, providing new insights into potential applications treatment metabolic disorder.

Language: Английский

Citations

2
Fat-1 ameliorates MAFLD and atherosclerosis through promoting the nuclear localization of PPARα in hamsters DOI Creative Commons
Wenxi Zhang, Jiabao Guo,

Guolin Miao

et al.

Research, Journal Year: 2024, Volume and Issue: 8

Published: Dec. 21, 2024

Fat-1, an enzyme encoded by the fat-1 gene, is responsible for conversion of endogenous omega-6 polyunsaturated fatty acids into omega-3 in Caenorhabditis elegans. To better investigate whether expression Fat-1 will exert a beneficial function dyslipidemia and metabolic dysfunction-associated liver disease (MAFLD), we established adeno-associated virus 9 expressing Fat-1. We found that adeno-associated-virus-mediated markedly reduced levels plasma triglycerides total cholesterol but increased high-density lipoprotein male wild-type hamsters on both chow diet high-fat as well chow-diet-fed LDLR-/- hamsters. ameliorated diet-induced MAFLD enhancing acid oxidation through hepatic peroxisome proliferator-activated receptor α (PPARα)-dependent pathway. Mechanistically, multiple lipid derivatives ligands PPARα simultaneously facilitated nuclear localization PPARα. Our results provide new insights therapeutic potentials to treat dyslipidemia, MAFLD, atherosclerosis.

Language: Английский

Citations

0