Bilirubin, a hepatoprotective agent that activates SIRT1, PGC-1α, and PPAR-α, while inhibiting NF-κB in rats with metabolic-associated fatty liver disease DOI Creative Commons
Motahareh Taghizadeh, Mohammad Hasan Maleki, Omid Vakili

et al.

Scientific Reports, Journal Year: 2024, Volume and Issue: 14(1)

Published: Nov. 25, 2024

Metabolic-associated fatty liver disease (MAFLD) is a chronic disorder characterized by alongside overweight or obesity and/or type 2 diabetes mellitus (T2DM). Timely intervention crucial for potential cure. This study aimed to investigate the effects of bilirubin, an endogenous antioxidant, on lipid metabolism and inflammation in MAFLD. Specifically, it examined bilirubin's impact SIRT1, PPAR-α, NF-κB livers rats with MAFLD induced high-fat diet (HFD) streptozotocin (STZ) administration. Forty eight-week adult male Sprague Dawley were divided into five groups (n = 8): Control, HFD-STZ, HFD-S-BR6, HFD-S-BR14, C-BR14. In last three groups, bilirubin administration was performed intraperitoneally 6 14 weeks (10 mg/kg/day). We selected key genes associated subsequently GO (Gene Ontology) KEGG (Kyoto Encyclopedia Genes Genomes) analyses explore enriched biological processes signaling pathways. Hence, gene expression PGC-1α, inflammatory (NF-κB, TNF-α, IL-6, IL-1β) measured using Real-time quantitative PCR. Stereological histopathological alterations structure as well profile, biochemical indices, also assessed among different groups. The enrichment analysis identified that several pathways might be related Bilirubin-treated contained higher SIRT1 levels approximately 5.7-, 2.1-, 2.2-fold, respectively, compared HFD-receiving (p < 0.0001, p 0.05, 0.05). Whereas, involved cascades, including NF-κB, downregulated 0.6-fold 0.05) following 14-week treatment while only significantly decreased IL-6 (approximately 0.6-fold, observed after 6-week bilirubin. Remarkably, favorably reversed HFD liver's volume cell numbers ameliorated structural changes. It improved parameters, indices HFD-STZ rats. indicated acts protective/ameliorative compound against MAFLD, particularly through regulating

Language: Английский

Diet and physical exercise as key players to tackle MASLD through improvement of insulin resistance and metabolic flexibility DOI Creative Commons
Sara Paola Mambrini,

Antônio Grillo,

Santo Colosimo

et al.

Frontiers in Nutrition, Journal Year: 2024, Volume and Issue: 11

Published: Aug. 20, 2024

Metabolic Dysfunction-Associated Steatotic Liver Disease (MASLD) has emerged as a prevalent health concern, encompassing wide spectrum of liver-related disorders. Insulin resistance, key pathophysiological feature MASLD, can be effectively ameliorated through dietary interventions. The Mediterranean diet, rich in whole grains, fruits, vegetables, legumes, and healthy fats, shown promising results improving insulin sensitivity. Several components the such monounsaturated fats polyphenols, exert anti-inflammatory antioxidant effects, thereby reducing hepatic steatosis inflammation. Furthermore, this pattern been associated with higher likelihood achieving MASLD remission. In addition to modifications, physical exercise, particularly resistance plays crucial role enhancing metabolic flexibility. Resistance exercise training promotes utilization fatty acids an energy source. It enhances muscle glucose uptake glycogen storage, thus burden on liver excess blood glucose. stimulates protein synthesis, contributing improved muscle-to-fat ratio overall health. When implemented synergistically, diet elicit complementary effects combating MASLD. Combined interventions have demonstrated additive benefits, including greater improvements increased flexibility, enhanced potential for This underscores importance adopting multifaceted approach modifications regular manage narrative review explores biological mechanisms addressing by targeting decreased

Language: Английский

Citations

11
Different Coactivator Recruitment to Human PPARα/δ/γ Ligand-Binding Domains by Eight PPAR Agonists to Treat Nonalcoholic Fatty Liver Disease DOI Creative Commons
S Kamata,

Akihiro Honda,

Nonoka Kashiwagi

et al.

Biomedicines, Journal Year: 2024, Volume and Issue: 12(3), P. 624 - 624

Published: March 11, 2024

Three peroxisome proliferator-activated receptor subtypes, PPARα, PPAR(ß/)δ, and PPARγ, exert ligand-dependent transcriptional control in concert with retinoid X receptors (RXRs) on various gene sets harboring PPAR response elements (PPREs) their promoter regions. Ligand-bound PPAR/RXR complexes do not directly regulate transcription; instead, they recruit multiprotein coactivator to specific genomic regulatory loci cooperatively activate transcription. Several coactivators are expressed a single cell; however, ligand-bound can be associated only one through consensus LXXLL motif. Therefore, altered transcription induced by subtypes/agonists may attributed the recruitment of species. Using time-resolved fluorescence resonance energy transfer assay, we analyzed four peptides (PGC1α, CBP, SRC1, TRAP220) human PPARα/δ/γ-ligand-binding domains (LBDs) using eight dual/pan agonists (bezafibrate, fenofibric acid, pemafibrate, pioglitazone, elafibranor, lanifibranor, saroglitazar, seladelpar) that are/were anticipated treat nonalcoholic fatty liver disease. These all recruited PPARα/γ-LBD varying potencies efficacy. Only five PPARδ-LBD, concentration-dependent responses differed from those PPARα/γ-LBD. results indicate expression PPREs different caused, part, coactivators, which responsible for unique pharmacological properties these agonists.

Language: Английский

Citations

6
Alternative Splicing Events and Differently Expressed Genes During Peak Mortality in Large Yellow Croaker (Larimichthys crocea) Infected with Scuticociliate DOI Creative Commons
Jian Jin, Yang Li, Xiande Liu

et al.

Marine Biotechnology, Journal Year: 2025, Volume and Issue: 27(1)

Published: Jan. 21, 2025

Language: Английский

Citations

0
Therapeutic Potential and Challenges of Pioglitazone in Cancer Treatment DOI Creative Commons
Maria Vasileiou, Sotirios Charalampos Diamantoudis, Christina Tsianava

et al.

Applied Sciences, Journal Year: 2025, Volume and Issue: 15(4), P. 1925 - 1925

Published: Feb. 13, 2025

Pioglitazone (ACTOS) is a thiazolidinedione for peroxisome proliferator-activated receptor γ (PPAR-γ) that has been well established the second or third line treatment of type 2 diabetes mellitus. Beyond effects on glucose metabolism, pioglitazone displays positive lipid blood pressure, endothelial function, bone density, and apoptosis cancer cells. In fact, according to in vitro experiments preclinical studies, PPAR-γ ligand currently considered potential target both chemoprevention therapy. ligands are known inhibit cell proliferation metastasis through terminal differentiation underexpression inflammatory mediators. Despite its anticancer properties, was withdrawn by national medicine agencies France Germany, due reports increased incidence bladder cancer. These were associated with European populations undergoing higher doses longer durations treatment. this review, we discuss pharmacokinetics, therapeutic potential, limitations regarding clinical use pioglitazone, focus

Language: Английский

Citations

0
Effects of Quercetin Metabolites on Glucose‐Dependent Lipid Accumulation in 3T3‐L1 Adipocytes DOI Creative Commons
Marco Rendine, Samuele Venturi, Mirko Marino

et al.

Molecular Nutrition & Food Research, Journal Year: 2025, Volume and Issue: unknown

Published: April 21, 2025

ABSTRACT The aim of the study was to assess effects quercetin metabolites (QMs) on lipid accumulation in adipocytes under high‐glucose and physiological‐glucose concentrations elucidate mechanisms involved. 3T3‐L1 mature were exposed a physiological glucose concentration, as model caloric restriction (CR), or high (control), with without QMs (quercetin‐3‐glucuronide [Q3G] isorhamnetin [ISOR]). Cells treated Q3G (0.3 0.6 µmol/L) ISOR (0.2 0.4 for 48 h. Lipid (Oil Red O staining) Δ level (HPLC) assessed. Under glucose, reduced (−10.8% −10.4%; p < 0.01) (−13.6% −14.2%; 0.05). CR, increased (+21.6% +21% ISOR; pAMPK levels (+1.4‐fold; (+1.4‐ +1.5‐fold; 0.05), while upregulated SIRT1 PGC‐1α (+2.3‐ Findings support, first time, potential contribution QMs, especially ISOR, regulation metabolism vitro, possibly via AMPK activation. Further studies, including vivo, are encouraged strengthen evidence observed.

Language: Английский

Citations

0
Targeting the UCP1-dependent thermogenesis pathway with CRISPR/Cas9: a new approach to obesity management DOI Creative Commons

Esmail Karami,

Fatemeh Rostamkhani, Mohammad Reza Abdollahi

et al.

Current Research in Biotechnology, Journal Year: 2025, Volume and Issue: unknown, P. 100295 - 100295

Published: May 1, 2025

Language: Английский

Citations

0
Anti-steatotic effects of PPAR-alpha and gamma involve gut-liver axis modulation in high-fat diet-fed mice DOI
Isabela Macedo Lopes Vasques‐Monteiro, Aline Fernandes‐da‐Silva, Carolline Santos Miranda

et al.

Molecular and Cellular Endocrinology, Journal Year: 2024, Volume and Issue: 585, P. 112177 - 112177

Published: Feb. 17, 2024

Language: Английский

Citations

3
Identification of phytochemicals as putative ligands for the targeted modulation of peroxisome proliferator‐activated receptor α (PPARα) in animals DOI
Faiz‐ul Hassan, Muhammad Saif-ur Rehman, Maryam Javed

et al.

Journal of Biomolecular Structure and Dynamics, Journal Year: 2023, Volume and Issue: unknown, P. 1 - 12

Published: Oct. 14, 2023

The PPAR family of transcription factors are ligand-activated and regulate diverse functions including metabolic, neurological, inflammatory diseases, neurodegenerative disorders, fertility or reproduction in the body. Specifically, PPARα is known to play a role reducing levels circulating triglycerides regulating energy homeostasis livestock animals. This study aimed identify phytochemicals that could serve as ligands for modulation bovine nuclear peroxisome proliferator-activated receptor alpha (PPARα) using molecular docking studies. Therefore, we investigated 1000 flavonoids belonging different groups their ability bind docking. Out 1000, 6 top lead compounds with maximum binding affinity, evaluated through docking, were further analysed physicochemical properties drug-likeness attributes. results revealed two flavonoids, Quercetin-3-o-rhamnoside (-)- epicatechingallate, which fatty acid synthase inhibitors, demonstrated high scores (-8.66 kcal/mol -8.49 kcal/mol, respectively) low RMSD values (1.61 1.28 compared agonist (

Language: Английский

Citations

7
mTORC2 knockdown mediates lipid metabolism to alleviate hyperlipidemic pancreatitis through PPARα DOI
Xiang-Yang Wang, Yilei Liu,

Yaxiong Zhou

et al.

Journal of Biochemical and Molecular Toxicology, Journal Year: 2024, Volume and Issue: 38(8)

Published: Aug. 1, 2024

Abstract Hyperlipidemic pancreatitis (HP) is an inflammatory injury of the pancreas triggered by elevated serum triglyceride (TG) levels. The mechanistic target rapamycin (mTOR) signaling pathway plays a crucial role in regulating lipid homeostasis and inflammation. This study aimed to investigate whether activity mTOR complex 2 (mTORC2) affects progression HP its underlying mechanisms. In vivo, high‐fat diet retrograde administration sodium taurocholate were employed establish models rats, with pancreatic tissue pathology evaluated. expression Rictor peroxisome proliferator‐activator receptor (PPAR) was examined. levels TG, fatty acid metabolites, metabolism‐related factors determined. vitro, acinar cells (PACs) exposed palmitic cholecystokinin‐8. PAC apoptosis, pyroptosis, ferroptosis assessed. models, rats PACs exhibited upregulated downregulated PPARα, knockdown promoted PPARα expression. decreased α‐amylase, total cholesterol, low‐density lipoprotein lactate dehydrogenase, factors, while increasing high‐density cholesterol increased ACOX1 CPT1α SREBP‐1, CD36, SCD1, ACLY, ACACA. reduced damage structure. inhibited ferroptosis. Treatment antagonist GW6471 abolished beneficial effects knockdown. Rictor/mTORC2 deficiency reduces TG levels, maintains homeostasis, suppresses inflammation inhibiting Weakening mTORC2 holds promise as novel therapeutic strategy for HP.

Language: Английский

Citations

2
Effects of bile acids supplementation in feed on digestive capacity, antioxidant capacity, lipid metabolism, and intestinal microorganisms in Yellow River carp (Cyprinus carpio) DOI Creative Commons
Yun Zhao,

Chen Wang,

Yaling Li

et al.

Aquaculture Reports, Journal Year: 2024, Volume and Issue: 36, P. 102096 - 102096

Published: April 16, 2024

This study investigated the effects of adding bile acids (BA) to feed on several biological aspects Yellow River carp (Cyprinus carpio). The experimental design covered four groups, namely, CT, BA1, BA2, and BA3, fed diets containing 0 mL/kg, 0.1 1.0 10.0 mL/kg BA, respectively, with an initial body weight 46.13±0.74 g were for 28 days. results revealed that BA increased trypsin lipase activities, positively influencing growth performance. Additionally, it enhanced activity intestinal antioxidant-related enzymes expression related genes. Meanwhile, our findings suggested addition might restrict hepatic lipid deposition by inhibiting lipogenesis-related genes stimulating lipolysis-related Furthermore, significantly altered microorganisms' flora structure, leading a decrease in relative abundance Proteobacteria.

Language: Английский

Citations

1