Potential Therapeutic Exploitation of G Protein-Coupled Receptor 120 (GPR120/FFAR4) Signaling in Obesity-Related Metabolic Disorders

The increasing prevalence of overweight and obesity not only in adults but also among children and adolescents has become one of the most alarming health problems worldwide. Metabolic disorders accompanying fat accumulation during pathological weight gain induce chronic low-grade inflammation, which, in a vicious cycle, increases the immune response through pro-inflammatory changes in the cytokine (adipokine) profile. Obesity decreases life expectancy, largely because obese individuals are at an increased risk of many medical complications, often referred to as metabolic syndrome, which refers to the co-occurrence of insulin resistance (IR), impaired glucose tolerance, type 2 diabetes (T2D), atherogenic dyslipidemia, hypertension, and premature ischemic heart disease. Metabotropic G protein-coupled receptors (GPCRs) constitute the most numerous and diverse group of cell surface transmembrane receptors in eukaryotes. Among the GPCRs, researchers are focusing on the connection of G protein-coupled receptor 120 (GPR120), also known as free fatty acid receptor 4 (FFAR4), with signaling pathways regulating the inflammatory response and insulin sensitivity. This review presents the current state of knowledge concerning the involvement of GPR120 in anti-inflammatory and metabolic signaling. Since both inflammation in adipose tissue and insulin resistance are key problems in obesity, there is a rationale for the development of novel, GPR120-based therapies for overweight and obese individuals. The main problems associated with introducing this type of treatment into clinical practice are also discussed.