Evaluation of G-protein coupled receptor (GPR-120) agonist effect in intestinal and hepatic alterations induced in mice after administation oh a high-fat and high-carbohydrate diet (WSD).

Obesity and related metabolic diseases (type II diabetes, dyslipidemia, cardiovascular diseases, steatosis and non-alcoholic steatohepatitis and intestinal disfunction) represent a problem of global importance (1). Increasingly evidences demonstrates that the type of diet and the quantity of fatty acids (FFAs) play a key role in the onset and progression of these unresolved pathologies. FFAs represent the ligands of the G protein-coupled receptors (GPCRs). Among the GPCRs, the G protein-coupled receptor (GPR)-120 is involved in the appetite control, body weight regulation, adipogenesis, maintenance of energy homeostasis, chronic inflammation, and insulin resistance and fibrosis (2). The aim of the project is to evaluate the potential beneficial effect of a new synthetic agonist of GPR-120 (GprA), in the progression of the dietinduced alterations in the intestinal wall and the liver parenchyma. We monitored the progression of liver and intestinal damages in mice fed for 26 and 30 weeks with a “Western style” diet (WSD) and treated daily by oral gavage with 3 doses (30-60-90 mg/Kg) of GprA. The analyses in the liver highlighted that GprA at 90mg/Kg can attenuate the progression of steatosis both at the histological and molecular levels. Furthermore, at 30w, GprA is also effective in the reduction of collagen maturation and deposition, and expression of connective tissue growth factor (CTGF). Regarding the intestine, evaluations on both small and large intestine has been conducted. Macroscopic and histological features (villi length, crypt depth and collagen deposition) and gene expression (perilipin 2, mucin 2, zonulin 1 and CD68) did not highlighted clear effects of GprA on small intestine, as well as on colon. Altogether, our data confirm the role of FFAR4 in liver alterations driven by a high fat diet, revealing that GprA represents a candidate for the development of a new therapeutic approach at least in the steatohepatitis.