Targeting SREBPs for treatment of the metabolic syndrome

Trends Pharmacol Sci. 2015 Jun;36(6):406-16. doi: 10.1016/j.tips.2015.04.010. Epub 2015 May 21.

Abstract

Over the past few decades, mortality resulting from cardiovascular disease (CVD) steadily decreased in western countries; however, in recent years, the decline has become offset by the increase in obesity. Obesity is strongly associated with the metabolic syndrome and its atherogenic dyslipidemia resulting from insulin resistance. While lifestyle treatment would be effective, drugs targeting individual risk factors are often required. Such treatment may result in polypharmacy. Novel approaches are directed towards the treatment of several risk factors with one drug. Studies in animal models and humans suggest a central role for sterol regulatory-element binding proteins (SREBPs) in the pathophysiology of the metabolic syndrome. Four recent studies targeting the maturation or transcriptional activities of SREBPs provide proof of concept for the efficacy of SREBP inhibition in this syndrome.

Keywords: SREBP inhibitors; SREBPs; insulin resistance; metabolic syndrome.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Humans
  • Metabolic Syndrome / drug therapy
  • Metabolic Syndrome / genetics
  • Metabolic Syndrome / metabolism*
  • Protein Kinase Inhibitors / pharmacology
  • Protein Kinase Inhibitors / therapeutic use
  • Pyridines / pharmacology
  • Pyridines / therapeutic use
  • Sterol Regulatory Element Binding Proteins / antagonists & inhibitors*
  • Sterol Regulatory Element Binding Proteins / genetics
  • Sterol Regulatory Element Binding Proteins / metabolism
  • Thiazoles / pharmacology
  • Thiazoles / therapeutic use
  • Triterpenes / pharmacology
  • Triterpenes / therapeutic use

Substances

  • Protein Kinase Inhibitors
  • Pyridines
  • Sterol Regulatory Element Binding Proteins
  • Thiazoles
  • Triterpenes
  • fatostatin
  • betulin