title: Targeting SREBPs for treatment of the metabolic syndrome.
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.
authors.affiliation: Institute of Pharmacology and Toxicology, Paracelsus Medical University, Salzburg, Austria.
authors.forename: Selma M
authors.initials: SM
authors.lastname: Soyal
authors.affiliation: Institute of Pharmacology and Toxicology, Paracelsus Medical University, Salzburg, Austria.
authors.forename: Charity
authors.initials: C
authors.lastname: Nofziger
authors.affiliation: Institute of Pharmacology and Toxicology, Paracelsus Medical University, Salzburg, Austria.
authors.forename: Silvia
authors.initials: S
authors.lastname: Dossena
authors.affiliation: Institute of Pharmacology and Toxicology, Paracelsus Medical University, Salzburg, Austria.
authors.forename: Markus
authors.initials: M
authors.lastname: Paulmichl
authors.affiliation: Institute of Pharmacology and Toxicology, Paracelsus Medical University, Salzburg, Austria. Electronic address: wolfgang.patsch@pmu.ac.at.
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Patsch
mesh_terms: D000818:Animals; D006801:Humans; D024821:Metabolic Syndrome / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism*; D047428:Protein Kinase Inhibitors / Q000494:pharmacology / Q000627:therapeutic use; D011725:Pyridines / Q000494:pharmacology / Q000627:therapeutic use; D051779:Sterol Regulatory Element Binding Proteins / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism; D013844:Thiazoles / Q000494:pharmacology / Q000627:therapeutic use; D014315:Triterpenes / Q000494:pharmacology / Q000627:therapeutic use; D000094062:Betulinic Acid
chemical_list: D047428:Protein Kinase Inhibitors; D011725:Pyridines; D051779:Sterol Regulatory Element Binding Proteins; D013844:Thiazoles; D014315:Triterpenes; C545733:fatostatin; C002503:betulin; D000094062:Betulinic Acid
keywords: SREBP inhibitors; SREBPs; insulin resistance; metabolic syndrome