Targeting the liver in the metabolic syndrome: Evidence from animal models

Michele Petruzzelli, Guiseppe Lo Sasso, Piero Portincasa, Giuseppe Palasciano, Antonio Moschetta

Research output: Contribution to journalReview articlepeer-review

26 Scopus citations


The metabolic syndrome is an emerging global epidemic characterized by clustering of metabolic abnormalities leading to increased cardiovascular risk: glucose intolerance or type 2 diabetes, dyslipidemia, hypertension, and "central" obesity. Scientists are decoding and piecing together the molecular texture underlying the metabolic syndrome: insulin resistance and dyslipidemia stand out as central pathophysiological events. In this picture, the liver rises as the leading organ in the maintenance of metabolic fitness; it serves as the first relay station for processing dietary information, and encloses the whole biochemical machinery for both glucose and lipid storage and disposal. In addition, the liver is a target of the different endocrine molecules secreted by pancreatic β-cells and adipose tissue. Evidence collected in animal models supports the central role of the liver in the metabolic syndrome. While specific bereft of insulin sensitivity in skeletal muscle and adipose tissue fails to induce diabetes at certain extent, this is constantly the outcome in case of hepatic insulin resistance. Also, dyslipidemia is currently interpreted as the result of increased flux of free fatty acids to the liver with ensuing misbalance of lipoprotein synthesis and removal. In this review we bring together recent advances in the field of lipid sensing nuclear receptors, adipokines and other molecules responsible for metabolic fitness, and provide a putative coherent frame to conceive the pathophysiology of the metabolic syndrome.

Original languageEnglish (US)
Pages (from-to)2199-2207
Number of pages9
JournalCurrent Pharmaceutical Design
Issue number21
StatePublished - Jul 2007


  • Adipokines
  • Gene therapy
  • Liver
  • Metabolic syndrome
  • Mouse models
  • Nuclear receptors

ASJC Scopus subject areas

  • Pharmacology
  • Drug Discovery


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