Background And Aims: Butyric acid is an intestinal microbiota-produced short-chain fatty acid, which exerts salutary effects on alleviating nonalcoholic fatty liver disease (NAFLD). However, the underlying mechanism of butyrate on regulating hepatic lipid metabolism is largely unexplored.
Methods: A mouse model of NAFLD was induced with high-fat diet feeding, and sodium butyrate (NaB) intervention was initiated at the eighth week and lasted for 8 weeks. Hepatic steatosis was evaluated and metabolic pathways concerning lipid homeostasis were analyzed.
Results: Here, we report that administration of NaB by gavage once daily for 8 weeks causes an augmentation of insulin-induced gene (Insig) activity and inhibition of lipogenic gene in mice fed with high-fat diet. Mechanistically, NaB is sufficient to enhance the interaction between Insig and its upstream kinase AMP-activated protein kinase (AMPK). The stimulatory effects of NaB on Insig-1 activity are abolished in AMPKα1/α2 double knockout (AMPK-/-) mouse primary hepatocytes. Moreover, AMPK activation by NaB is mediated by LKB1, as evidenced by the observations showing NaB-mediated induction of phosphorylation of AMPK, and its downstream target acetyl-CoA carboxylase is diminished in LKB1-/- mouse embryonic fibroblasts.
Conclusions: These studies indicate that NaB serves as a negative regulator of hepatic lipogenesis in NAFLD and that NaB attenuates hepatic steatosis and improves lipid profile and liver function largely through the activation of LKB1-AMPK-Insig signaling pathway. Therefore, NaB has therapeutic potential for treating NAFLD and related metabolic diseases.
Download full-text PDF |
Source |
|---|---|
| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8346675 | PMC |
| http://dx.doi.org/10.1016/j.jcmgh.2021.05.006 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Hepatitis C virus-free endoscope procedures project: An in-hospital elimination approach.
Kaohsiung J Med Sci
January 2025
Hepatobiliary Division, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan.
Hepatitis C virus (HCV) elimination in the care cascades for patients receiving invasive procedures remains elusive. This study aimed to evaluate the efficacy of HCV-free Endoscope Procedures Project (CEPP) in the effort toward hospital HCV micro-elimination in Taiwan. An electronic medical record (EMR)-based remind system was introduced into gastrointestinal, surgical, urological, and gynecological departments prior to the endoscopy procedures.
View Article and Find Full Text PDFThyromimetics and MASLD: Unveiling the Novel Molecules Beyond Resmetirom.
J Gastroenterol Hepatol
January 2025
Department of Pharmacology, Hepatology and Molecular Medicine Lab, Saveetha Dental College and Hospitals, Saveetha Institute of Medical and Technical Sciences (SIMATS), Chennai, Tamil Nadu, India.
Background: Resmetirom, the first FDA-approved drug for nonalcoholic steatohepatitis (NASH) with fibrosis in obese patients, when combined with lifestyle modifications, improves NASH resolution and reduces fibrosis by at least one stage. Low thyroid hormone (T) levels are linked to a higher risk of developing metabolic dysfunction-associated steatotic liver disease (MASLD). Epidemiological studies have confirmed the positive correlation between hypothyroidism and MASLD.
View Article and Find Full Text PDFAssociation of diet quality scores with risk of metabolic-associated fatty liver disease in Iranian population: a nested case-control study.
J Diabetes Metab Disord
June 2025
Gastroenterology and Liver Disease Research Center, Research Institute for Gastroenterology and Liver Disease, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
Background And Aim: A healthy diet has been recommended for non-alcoholic fatty liver disease (NAFLD). We aim to investigate the associations of diet quality indices with the risk of developingmetabolic-associated fatty liver disease (MAFLD).
Methods: We conducted this nested case-control study by recruiting 968 cases with MAFLD and 964 controls from the participants of the baseline phase of the Sabzevar Persian Cohort Study (SPCS).
Endogenous C-type natriuretic peptide offsets the pathogenesis of steatohepatitis, hepatic fibrosis, and portal hypertension.
PNAS Nexus
January 2025
Faculty of Medicine and Dentistry, William Harvey Research Institute, Barts and The London, Queen Mary University of London, Charterhouse Square, London EC1M 6BQ, United Kingdom.
Metabolic dysfunction-associated steatotic liver disease (MASLD), hepatic fibrosis, and portal hypertension constitute an increasing public health problem due to the growing prevalence of obesity and diabetes. C-type natriuretic peptide (CNP) is an endogenous regulator of cardiovascular homeostasis, immune cell reactivity, and fibrotic disease. Thus, we investigated a role for CNP in the pathogenesis of MASLD.
View Article and Find Full Text PDFALOX15 Aggravates Metabolic Dysfunction-Associated Steatotic Liver Disease in Mice with Type 2 Diabetes via Activating the PPARγ/CD36 Axis.
Antioxid Redox Signal
January 2025
Department of Pharmacology, School of Basic Medical Sciences, Xi'an Jiaotong University Health Science Center, Xi'an, Shaanxi, China.
Metabolic dysfunction-associated steatotic liver disease (MASLD) is a prevalent hepatic disorder worldwide. Arachidonic acid 15-lipoxygenase (ALOX15), an enzyme catalyzing the peroxidation of polyunsaturated fatty acids, plays a crucial role in various diseases. Here, we sought to investigate the involvement of ALOX15 in MASLD.
View Article and Find Full Text PDFWant AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!