engleski

Incretin based therapies-a novel treatment approach for non-alcoholic fatty liver disease

Non-alcoholic fatty liver disease (NAFLD) affects up to 30% of general population worldwide. Although the etiology is still unclear, it is considered as a hepatic manifestation of metabolic syndrome (MS), a condition closely linked to obesity and type 2 diabetes (T2DM). The current treatment of NAFLD principally include ameliorating MS components including weight loss, insulin sensitivity and serum lipids improvement by lifestyle modifications. Lack of success in implementing and sustaining lifestyle modifications arises the need for effective pharmacological agent in fatty liver treatment. Incretins are gut derived hormones which are secreted into the circulation in response to nutrient ingestion and enhance glucose-stimulated insulin secretion. Glucagon-like peptide-1 (GLP-1) is most important incretin hormone and a peptide of great interest in T2DM treatment. As circulating GLP-1 has a half-life about 1-2 minutes due to rapid degradation by enzyme dipeptidyl peptidase-4 (DPP4), GLP-1 receptor agonists with increased DPP4 resistance and DPP4 inhibitors have been developed. DPP4 serum activity and hepatic expression are shown to be elevated in several hepatic diseases which resulted in several experimental and clinical trials exploring the efficacy of incretin based therapies in NAFLD treatment. These studies suggest that GLP-1 analogues might have beneficial effect on hepatic steatosis acting as insulin sensitizers and directly by stimulating GLP-1 receptors expressed on hepatocytes. The use of DPP4 inhibitors also results in hepatic fat reduction but the mechanism of action remains unclear. In conclusion, there is growing evidence that incretin based therapies have beneficial effects on hepatocytes, however further study analysis are needed in order to aces the long term effect of incretin based therapies on NAFLD.

non-alcoholic fatty liver disease; insulin resistance; glucagon-like peptide-1; dipeptidyl peptidase-4 inhibitors

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