title: The metabolic syndrome: how it may influence hepatic stellate cell activation and hepatic fibrosis.
abstract: OBJECTIVE
  To highlight the metabolic or inflammatory components, deregulated in or pathogenic for the metabolic syndrome, that may, directly or indirectly, modulate hepatic fibrogenesis.
  
  
  RESULTS
  Advanced glycation end products signal profibrogenetic transformation of hepatic stellate cells. Altered adipocytokines favor insulin resistance and steatosis. They participate to the proinflammatory status of the metabolic syndrome. Among them, leptin has been shown to directly enhance fibrogenesis, whereas adiponectin has shown antifibrotic properties. The renin-angiotensin system, a component of arterial hypertension, is activated in the diseased liver, and there is convincing evidence that blockade of angiotensin II signaling attenuates fibrosis. Endocannabinoids, whose hepatic production and signaling capability are increased with insulin resistance and obesity, signal profibrotic response via the preponderant receptor, cannabinoid receptor 1, whereas antifibrotic and anti-inflammatory signals are rather generated via stimulation of cannabinoid receptor 2. Finally, recent data demonstrate that modulation of innate immunity, particularly modulation of natural killer and natural killer T cells, has potential roles in the resolution of steatohepatitis and fibrosis.
  
  
  CONCLUSIONS
  Several features associated with the metabolic syndrome can undoubtedly modulate liver fibrosis. More studies are needed to identify those that are prominent determinants of fibrosis in the metabolic syndrome and the benefit of their targeting for fibrosis prevention and treatment.
authors.affiliation: Laboratory of Gastroenterology, Université catholique de Louvain, Brussels, Belgium.
authors.forename: Nicolas
authors.initials: N
authors.lastname: Lanthier
authors.forename: Yves
authors.initials: Y
authors.lastname: Horsmans
authors.forename: Isabelle A
authors.initials: IA
authors.lastname: Leclercq
mesh_terms: D052242:Adiponectin / Q000378:metabolism; D017127:Glycation End Products, Advanced / Q000378:metabolism; D006801:Humans; D007328:Insulin / Q000378:metabolism; D036341:Intercellular Signaling Peptides and Proteins / Q000378:metabolism; D020738:Leptin / Q000378:metabolism; D008103:Liver Cirrhosis / Q000209:etiology / Q000378:metabolism / Q000517:prevention & control; D024821:Metabolic Syndrome / Q000378:metabolism* / Q000503:physiopathology*
chemical_list: D052242:Adiponectin; D017127:Glycation End Products, Advanced; D007328:Insulin; D036341:Intercellular Signaling Peptides and Proteins; D020738:Leptin