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

In the current modern era of unhealthy lifestyles, non-alcoholic fatty liver disease (NAFLD) is the most prevalent liver disease and has become a serious global health problem. To date, there is no approved pharmacotherapy for the treatment of NAFLD, and necessary lifestyle changes such as weight loss, diet, and exercise are usually not sufficient to manage this disease. Patients with type 2 diabetes mellitus (T2DM) have a significantly higher risk of developing NAFLD and vice versa. Sodium–glucose cotransporter 2 (SGLT2) inhibitors are antidiabetic agents that have recently been approved for two other indications: chronic kidney disease and heart failure in diabetics and non-diabetics. They are also emerging as promising new agents for NAFLD treatment, as they have shown beneficial effects on hepatic inflammation, steatosis, and fibrosis. Studies in animals have reported favorable effects of SGLT2 inhibitors, and studies in patients also found positive effects on body mass index (BMI), insulin resistance, glucose levels, liver enzymes, apoptosis, and transcription factors. There are some theories regarding how SGLT2 inhibitors affect the liver, but the exact mechanism is not yet fully understood. Therefore, biomarkers to evaluate underlying mechanisms of action of SGLT2 inhibitors on the liver have now been scrutinized to assess their potential as a future in-label therapy for NAFLD. In addition, finding suitable non-invasive biomarkers could be helpful in clinical practice for the early detection of NAFLD in patients. This is crucial for a positive disease outcome. The aim of this review is to provide an overview of the most recent findings on the effects of SGLT2 inhibitors on NAFLD biomarkers and the potential of SGLT2 inhibitors to successfully treat NAFLD.

Background and Objectives: In recent years, numerous studies have investigated and analyzed the levels of molecular biomarkers of temporomandibular disorders (TMD) from various tissue samples and body fluids. However, no study has investigated gingival crevicular fluid (GCF) in TMD patients. The purpose of this study was to determine the concentrations of pro-inflammatory cytokines in GCF before and after stabilization splint (SS) therapy in patients with painful TMD, to investigate whether SS administration causes changes in the concentrations of pro-inflammatory cytokines. An additional aim was to investigate the relationship of GCF cytokine levels with chronic pain intensity and clinical parameters. Materials and Methods: This prospective cohort study included 36 patients who were diagnosed with painful TMD using the Diagnostic Criteria for TMD (DC/TMD). GCF samples were collected at baseline before SS treatment (T0) and at one month (T1) and three months (T2) after the start of therapy. Customized ProcartaPlex Multiplex assays from eBioscience (Invitrogen™, Thermo Fisher Scientific, Viena, Austria) were used for the quantitative analysis of pro-inflammatory cytokines (IL-1β, IL-6, IL-7, IL-8, IL-13, and TNF-α). Patients filled out Croatian versions of questionnaires for self-assessment from Axis II DK/TMP: Graded Chronic Pain Scale (v2) (GCPSv2) and Jaw Function Limitation Scale-20 (JFLS-20). Results: The results showed that the GCF levels of IL-7 (Friedman’s test, p = 0.008) and IL-13 (Friedman’s test, p = 0.003) were significantly decreased at T2. The GCF level of IL-13 was in negative correlation with chronic pain grade score at T2 (Rho = −0.333), while the GCF level of IL-8 was in positive correlation with mobility limitation (Rho = 0.382) at T1. Conclusions: The results indicate that SS therapy might have a role in reducing inflammation and that the GCF could be a valuable medium for assessing molecular biomarkers.