Liraglutide With Metformin Therapy Ameliorates Hepatic Steatosis and Liver Injury in a Mouse Model of Non-alcoholic Steatohepatitis

Abstract

Background/Aim: Non-alcoholic fatty liver disease is a major cause of liver-related morbidity and mortality. Metformin is a widely used medication and may have additional benefits beyond glycemic control. Liraglutide, a novel treatment for diabetes and obesity, also has beneficial effects on non-alcoholic steatohepatitis (NASH). Metformin and liraglutide have both benefited NASH treatment. However, no study has reported the effects of combination therapy with liraglutide and metformin on NASH. Materials and Methods: We investigated the in vivo effects of metformin and liraglutide on NASH in a methionine/choline-deficient (MCD) diet-fed C57BL/6JNarl mouse model. Serum triglyceride, alanine aminotransferase and alanine aminotransferase levels were documented. Histological analysis was performed according to the NASH activity grade. Results: After treatment with liraglutide and metformin, body weight loss improved, and the liver/body weight ratio decreased. The metabolic effects and liver injury improved. Liraglutide and metformin alleviated MCD-induced hepatic steatosis and injury. Histological analysis revealed that NASH activity was reduced. Conclusion: Our results provide evidence for the anti-NASH activity of liraglutide in combination with metformin. Liraglutide with metformin may offer the potential for a disease-modifying intervention for NASH.Non-alcoholic fatty liver disease (NAFLD) is emerging as a major cause of liver-related morbidity and mortality, with a global prevalence of 25.24% (1). It is linked to obesity, insulin resistance and metabolic syndrome, and its appearance ranges from fat accumulation to advanced fibrosis and cirrhosis (2). It is now widely recognized that NAFLD represents a continuum of liver damage, ranging from simple steatosis to non-alcoholic steatohepatitis (NASH), advanced fibrosis and cirrhosis (3, 4). The risk of developing NASH and fibrosis is significantly higher in patients with metabolic comorbidities, such as obesity, diabetes and dyslipidemia (5). While current treatment 1037

Glucagon-like Peptide 1, Glucose-Dependent Insulinotropic Polypeptide, and Glucagon Receptor Agonists in Metabolic Dysfunction-Associated Steatotic Liver Disease: Novel Medication in New Liver Disease Nomenclature

“…Besides semaglutide, liraglutide attenuated the gene expression of the lipogenic genes acetyl-CoA carboxylase (ACC) and fatty acid synthase (FAS) while mitigating the expression of pro-inflammatory cytokines or transcription factor, including TNF-α and nuclear factor κ-light chain-enhancer of activated B cell (NF-κB) in high-fat diet (HFD) mice with ApoE and adiponectin (Acrp30) knockdown background, thus preventing MASH progression [69]. Consistent with that, Chiu et al showed that treatment with liraglutide-and metformin-induced weight loss, reduced liver/body weight ratio, and ameliorated steatosis, liver injury, and MASH activity in a methionine/choline-deficient (MCD) diet-fed C57BL/6JNarl mouse model [70]. Of note, GLP-1 analogs induce the polarization of macrophages toward the M2 phenotype and, via that, induce the expression of anti-inflammatory molecules such as IL-10, CD163, and CD204 while concurrently reducing c-c motif chemokine ligand 2 (CCL-2) expression [71].…”

Genome‑wide association study and polygenic risk scores predict psoriasis and its shared phenotypes in Taiwan

“…P<0.05 was considered to indicate a statistically significant difference. Statistical analyses were performed using SPSS ( ; version 22) and R (version R 4.1.0) software ( 46 ).…”

Efficacy of HMJ-38, a new quinazolinone analogue, against the gemcitabine-resistant MIA-PaCa-2 pancreatic cancer cells

“…To determine the differences between two and multiple groups, SPSS version 25.0 (IBM, Corp.) was used to perform a one-way analysis of difference, followed by Dunnett’s test and Tukey’s post-hoc test. A statistically significant difference was defined as one with a P value of 0.05 [ 40 ].…”