NEW COMPOUNDS FOR THE TREATMENT OF METABOLIC SYNDROME

Metabolic syndrome (MetS) is characterised by the simultaneous presence of a group of cardiovascular risk factors, and is associated with the development of type 2 diabetes, dyslipidemias, cardiovascular disease and non-alcoholic fatty liver disease, among others. In addition, there is evidence that MS is linked to systemic inflammation, which appears to be the main trigger for its complications. In recent years, several treatments have been developed to treat metabolic disorders such as MS, based on selective agonists of peroxisome proliferator-activated receptors (PPARα and PPARγ). For example, PPARα agonists, fibrates, are used in the treatment of dyslipidaemias (hypertriglyceridaemia and other hyperlipidaemias); and PPARγ agonists, glitazones, are indicated for the treatment of type 2 diabetes. However, the limited effect of PPARα agonists on glucose metabolism, and the side effects (cardiovascular risk, hepatotoxicity and bladder cancer) associated with selective PPARγ activators have created a need for the development of new dual PPARα/γ or pan-PPAR agonists, with partial activity on PPARγ. Researchers at the University of Valencia and INCLIVA have developed a family of compounds based on quinolines and tetrahydroquinolines with pan-PPAR agonist activity capable of: • Promote lipid metabolism and minimise inflammation in metabolic disorders, probably preventing the development of cardiovascular complications. • Improve lipid and carbohydrate parameters in obese and diabetic mouse models.