Ferulic acid restores mitochondrial dynamics and autophagy via AMPK signaling pathway in a palmitate-induced hepatocyte model of metabolic syndrome DOI Creative Commons
Yitong Li,

Weiyang Zhao,

Ali Tahir Sair

et al.

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

Published: Aug. 16, 2024

Mitochondrial dysfunction, characterized by elevated oxidative stress, impaired energy balance, and dysregulated mitochondrial dynamics, is a hallmark of metabolic syndrome (MetS) its comorbidities. Ferulic acid (FA), principal phenolic compound found in whole grains, has demonstrated potential ameliorating stress preserving homeostasis. However, the influence FA on health within context MetS remains unexplored. Moreover, impact autophagy, which essential for maintaining homeostasis integrity, not fully understood. Here, we aimed to study mechanisms action regulating autophagy using palmitate-treated HepG2 hepatocytes as cell model. We that improved restoring redox balance optimizing including biogenesis fusion/fission ratio. Additionally, was shown recover activate AMPK-related signaling. Our results provide new insights into therapeutic mitochondria-targeting agent prevention treatment MetS.

Language: Английский

Glucagon-like peptide-1 receptor: mechanisms and advances in therapy DOI Creative Commons

Zhikai Zheng,

Zong Yao,

Yiyang Ma

et al.

Signal Transduction and Targeted Therapy, Journal Year: 2024, Volume and Issue: 9(1)

Published: Sept. 18, 2024

The glucagon-like peptide-1 (GLP-1) receptor, known as GLP-1R, is a vital component of the G protein-coupled receptor (GPCR) family and found primarily on surfaces various cell types within human body. This specifically interacts with GLP-1, key hormone that plays an integral role in regulating blood glucose levels, lipid metabolism, several other crucial biological functions. In recent years, GLP-1 medications have become focal point medical community due to their innovative treatment mechanisms, significant therapeutic efficacy, broad development prospects. article thoroughly traces developmental milestones drugs, from initial discovery clinical application, detailing evolution diverse along distinct pharmacological properties. Additionally, this paper explores potential applications agonists (GLP-1RAs) fields such neuroprotection, anti-infection measures, reduction inflammation, enhancement cardiovascular function. It provides in-depth assessment effectiveness GLP-1RAs across multiple body systems-including nervous, cardiovascular, musculoskeletal, digestive systems. includes integrating latest trial data delving into signaling pathways mechanisms. primary goal emphasize extensive benefits using treating spectrum diseases, obesity, non-alcoholic fatty liver disease (NAFLD), neurodegenerative musculoskeletal forms cancer. ongoing new indications for drugs offers promising prospects further expanding interventions, showcasing field.

Language: Английский

Citations

97
Autophagy and the unfolded protein response shape the non-alcoholic fatty liver landscape: decoding the labyrinth DOI
Zahra Dashti, Zeynab Yousefi,

Pouria Kiani

et al.

Metabolism, Journal Year: 2024, Volume and Issue: 154, P. 155811 - 155811

Published: Feb. 2, 2024

Language: Английский

Citations

18
Alternate‐day fasting enhanced weight loss and metabolic benefits over pair‐fed calorie restriction in obese mice DOI Open Access

Hadia Nawaz,

Haneul Lee, Sumin Kang

et al.

Obesity, Journal Year: 2025, Volume and Issue: unknown

Published: Feb. 4, 2025

Abstract Objective Both alternate‐day fasting (ADF) and calorie restriction (CR) are effective weight loss strategies. However, most individuals find it difficult to adhere CR. Furthermore, CR can induce an excessive of not only fat but also muscle mass. This study aimed compare the effects ADF pair‐feeding (PF) on metabolic pathways underlying obesity in mice with high‐fat diet (HFD)‐induced obesity. Methods Male C57BL/6N Tac ( n = 10 per group) were fed HFD for 8 weeks establish a diet‐induced model. Mice then continued either access food or PF next weeks. We measured body weight, adiposity, plasma biomarkers, molecular mechanisms involving lipolysis autophagy. Results resulted comparable loss. Compared PF, showed significant reduction liver hepatic triglyceride levels. significantly increased ketone levels white adipose tissue lipolysis. tended activate autophagy elongation autophagosome formation, which insignificant. Conclusions These findings indicated that is promising intervention diseases, potentially due its superior efficacy promoting ketogenesis compared PF.

Language: Английский

Citations

2
Liraglutide attenuates type 2 diabetes mellitus-associated non-alcoholic fatty liver disease by activating AMPK/ACC signaling and inhibiting ferroptosis DOI Creative Commons

Tingli Guo,

Wenhui Yan, Xin Cui

et al.

Molecular Medicine, Journal Year: 2023, Volume and Issue: 29(1)

Published: Sept. 28, 2023

Non-alcoholic fatty liver disease (NAFLD) is one of the most common complications type 2 diabetes mellitus (T2DM). The pathogenesis NAFLD involves multiple biological changes, including insulin resistance, oxidative stress, inflammation, as well genetic and environmental factors. Liraglutide has been used to control blood sugar. But impact liraglutide on T2DM-associated remains unclear. In this study, we investigated potential molecular mechanisms inhibiting ferroptosis for improves NAFLD.Mice were fed high-fat-diet injected with streptozotocin mimic gene expression in was analysed by RNA-seq. fast glucose measured during period ferrostatin-1 administration. Hematoxylin eosin staining evaluate pathological changes liver. occurrence hepatic lipid peroxidation vivo. mechanism inhibition vitro cell culture.Liraglutide not only improved metabolism, but also ameliorated tissue damage livers. Transcriptomic analysis indicated that regulates metabolism related signaling AMPK ACC. Furthermore, inhibitor rather than other death inhibitors rescued viability presence high glucose. Mechanistically, liraglutide-induced activation phosphorylated ACC, while compound C blocked liraglutide-mediated suppression ferroptosis. Moreover, restored function T2DM mice vivo.These findings indicate ameliorates NAFLD, which possibly through AMPK/ACC pathway

Language: Английский

Citations

35
Metabolic-Dysfunction Associated Steatotic Liver Disease -Its Pathophysiology, Association with Atherosclerosis and Cardiovascular Disease, and Ideal Treatments DOI Open Access
Hidekatsu Yanai,

Hiroki Adachi,

Mariko Hakoshima

et al.

Published: Sept. 18, 2023

Metabolic-dysfunction associated steatotic liver disease (MASLD) is a chronic that affects more than quarter of the global population, and increasing worldwide, due to pandemic obesity. Insulin resistance closely with development progression MASLD. Hepatic entry increased fatty acids (FA) released from adipose tissue, increase in FA synthesis reduced oxidation liver, hepatic overproduction triglyceride (TG)-rich lipoproteins may induce Since insulin also induces atherosclerosis, leading cause for death MASLD patients cardiovascular (CVD). Considering CVD determines prognosis patients, ideal therapeutic interventions should reduce body weight, improve coronary risk factors, addition an improvement functiom. Lifestyle modification such as diet exercise surgical bariatric surgery intragastric balloons have shown by reducing weight. Sodium glucose cotransporter 2 inhibitors (SGLT2i) glucagon-like peptide-1 receptor agonists (GLP-1RA) been factors suppress occurrence CVD. Both SGLT2i GLP-1 reported enzymes, steatosis fibrosis. We recently selective peroxisome proliferator-activated receptor-alpha (PPARα) modulator, pemafibrate, improved function. PPARα multiple anti-atherogenic properties. Here, we consider pathophysiology mechanisms action drugs, whether drugs combination therapy could be treatments

Language: Английский

Citations

25
Advances in management of metabolic dysfunction-associated steatotic liver disease: from mechanisms to therapeutics DOI Creative Commons
Yuxiao Jiang, Lili Wu,

Xiaopeng Zhu

et al.

Lipids in Health and Disease, Journal Year: 2024, Volume and Issue: 23(1)

Published: April 2, 2024

Abstract Metabolic dysfunction-associated steatotic liver disease (MASLD) is the leading cause of chronic that affects over 30% world’s population. For decades, heterogeneity non-alcoholic fatty (NAFLD) has impeded our understanding mechanism and development effective medications. However, a recent change in nomenclature from NAFLD to MASLD emphasizes critical role systemic metabolic dysfunction pathophysiology this therefore promotes progress pharmaceutical treatment MASLD. In review, we focus on underlying abnormality hepatic lipid metabolism patients with MASLD, summarize latest therapeutic medications target disorders.

Language: Английский

Citations

13
A quantitative weight-of-evidence method for confidence assessment of adverse outcome pathway networks: A case study on chemical-induced liver steatosis DOI
A. Verhoeven, J. van Ertvelde, Joost Boeckmans

et al.

Toxicology, Journal Year: 2024, Volume and Issue: 505, P. 153814 - 153814

Published: April 25, 2024

Language: Английский

Citations

9
Thyme, oregano, and rosemary: herbs and food supplements for the management of metabolic associated fatty liver disease DOI
Hamza Elbouny, Ayoub Amssayef,

Rania Benjamaa

et al.

Nutrire, Journal Year: 2025, Volume and Issue: 50(1)

Published: Jan. 6, 2025

Language: Английский

Citations

1
AlphaFold-Based AI Docking Reveals AMPK/SIRT1-TFEB Pathway Modulation by Traditional Chinese Medicine in Metabolic-Associated Fatty Liver Disease DOI Creative Commons

Lulu Zhang,

Yi Zheng, Mingyan Shao

et al.

Pharmacological Research, Journal Year: 2025, Volume and Issue: unknown, P. 107617 - 107617

Published: Jan. 1, 2025

Language: Английский

Citations

1
The Role of GLP1-RAs in Direct Modulation of Lipid Metabolism in Hepatic Tissue as Determined Using In Vitro Models of NAFLD DOI Creative Commons
Ana G. Petrovic, Dunja Igrec, Karla Rožac

et al.

Current Issues in Molecular Biology, Journal Year: 2023, Volume and Issue: 45(6), P. 4544 - 4556

Published: May 24, 2023

Glucagon-like peptide 1 receptor agonists (GLP-1RAs) have been shown to improve glucose and lipid homeostasis, promote weight loss, reduce cardiovascular risk factors. They are a promising therapeutic option for non-alcoholic fatty liver disease (NAFLD), the most common disease, associated with T2DM, obesity, metabolic syndrome. GLP-1RAs approved treatment of T2DM but not NAFLD. Most recent clinical trials suggested importance early pharmacologic intervention in alleviating limiting NAFLD, as well highlighting relative scarcity vitro studies on semaglutide, indicating need further research. However, extra-hepatic factors contribute GLP-1RA results vivo studies. Cell culture models NAFLD can be helpful eliminating extrahepatic effects alleviation hepatic steatosis, modulation metabolism pathways, reduction inflammation, prevention progression severe conditions. In this review article, we discuss role GLP-1 using human hepatocyte models.

Language: Английский

Citations

22