Lipid-sensing nuclear receptors in the pathophysiology and treatment of the metabolic syndrome

Wiley Interdiscip Rev Syst Biol Med. Sep-Oct 2011;3(5):562-87. doi: 10.1002/wsbm.137. Epub 2011 Feb 16.

Abstract

Metabolic syndrome (MS) is a cluster of different diseases, namely central obesity, hypertension, hyperglycemia, and dyslipidemia, together with a pro-thrombotic and pro-inflammatory state. These metabolic abnormalities are often associated with an increased risk for cardiovascular disease (CVD) and cancer. Dietary and lifestyle modifications are currently believed more effective than pharmacological therapies in the management of MS patients. Nevertheless, the relatively low grade of compliance of patients to these recommendations, as well as the failure of current therapies, highlights the need for the discovery of new pharmacological and nutraceutic approaches. A deeper knowledge of the patho-physiological events that initiate and support the MS is mandatory. Lipid-sensing nuclear receptors (NRs) are the master transcriptional regulators of lipid and carbohydrate metabolism and inflammatory responses, thus standing as suitable targets. This review focuses on the physiological relevance of the NRs (peroxisome proliferator-activated receptors, liver X receptors, and farnesoid X receptor) in the control of whole-body homeostasis, with a special emphasis on lipid and glucose metabolism, and on the relationships between metabolic unbalances, systemic inflammation, and the onset of CVD. Future perspectives and possible clinical applications are also presented.

Publication types

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

MeSH terms

  • Energy Metabolism
  • Fatty Acids / metabolism
  • Glucose / metabolism
  • Humans
  • Liver X Receptors
  • Metabolic Syndrome / etiology
  • Metabolic Syndrome / therapy*
  • Orphan Nuclear Receptors / metabolism
  • Peroxisome Proliferator-Activated Receptors / metabolism
  • Receptors, Cytoplasmic and Nuclear / metabolism*

Substances

  • Fatty Acids
  • Liver X Receptors
  • Orphan Nuclear Receptors
  • Peroxisome Proliferator-Activated Receptors
  • Receptors, Cytoplasmic and Nuclear
  • farnesoid X-activated receptor
  • Glucose