New therapeutic options for the metabolic syndrome: what's next?

Trends Endocrinol Metab. 2005 Aug;16(6):254-60. doi: 10.1016/j.tem.2005.06.001.

Abstract

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.

Publication types

  • Review

MeSH terms

  • Cardiovascular Diseases / etiology
  • Diabetes Mellitus, Type 2 / etiology
  • Fatty Acids / metabolism
  • Humans
  • Metabolic Syndrome / metabolism*
  • Metabolic Syndrome / therapy*
  • Trans-Activators / agonists*
  • Trans-Activators / metabolism*
  • Transcription Factors
  • Triglycerides / metabolism

Substances

  • Fatty Acids
  • Trans-Activators
  • Transcription Factors
  • Triglycerides
  • peroxisome-proliferator-activated receptor-gamma coactivator-1