New therapeutic options for the metabolic syndrome: what's next?
The metabolic syndrome (MSX), characterized by obesity, insulin resistance, dyslipidemia and hypertension, increases the risk of cardiovascular morbidity and mortality. It has recently been hypothesized that MSX and type 2 diabetes are caused by triglyceride and long-chain fatty acid accumulation in liver, muscle, pancreatic islets and selected brain areas. This lipocentric approach is integrated with analysis of inflammation associated with end-organ damage, including the vascular wall. Genes and proteins contributing to insulin resistance, beta cell dysfunction and vascular wall damage have been identified. Transcription factors and coactivators, including peroxisome proliferator-activated receptor gamma (PPARgamma) coactivator-1 are crucial in mediating insulin resistance and accelerating vascular wall inflammation, and represent promising therapeutic targets. New pharmacological strategies include dual PPARalpha/gamma agonists, drugs with pleiotropic effects or combination therapies.
Flordellis
Christodoulos S
CS
Department of Pharmacology, School of Medicine, University of Patras, 26110 Patras, Greece. flordell@med.upatras.gr
Ilias
Ioannis
I
Papavassiliou
Athanasios G
AG
D002318:Cardiovascular Diseases / Q000209:etiology; D003924:Diabetes Mellitus, Type 2 / Q000209:etiology; D005227:Fatty Acids / Q000378:metabolism; D006801:Humans; D024821:Metabolic Syndrome / Q000378:metabolism* / Q000628:therapy*; D015534:Trans-Activators / Q000819:agonists* / Q000378:metabolism*; D014157:Transcription Factors; D014280:Triglycerides / Q000378:metabolism
D005227:Fatty Acids; D015534:Trans-Activators; D014157:Transcription Factors; D014280:Triglycerides; C111264:peroxisome-proliferator-activated receptor-gamma coactivator-1