Oxidative stress-induced risk factors associated with the metabolic syndrome: a unifying hypothesis

Ignazio Grattagliano, Vincenzo O. Palmieri, Piero Portincasa, Antonio Moschetta, Giuseppe Palasciano

Research output: Contribution to journalReview articlepeer-review

234 Scopus citations


Although the biochemical steps linking insulin resistance with the metabolic syndrome have not been completely clarified, mounting experimental and clinical evidence indicate oxidative stress as an attractive candidate for a central pathogenic role since it potentially explains the appearance of all risk factors and supports the clinical manifestations. In fact, metabolic syndrome patients exhibit activation of biochemical pathways leading to increased delivery of reactive oxygen species, decreased antioxidant protection and increased lipid peroxidation. The described associations between increased abdominal fat storage, liver steatosis and systemic oxidative stress, the diminished concentration of nitric oxide derivatives and antioxidant vitamins and the endothelial oxidative damages observed in subjects with the metabolic syndrome definitively support oxidative stress as the common second-level event in a unifying pathogenic view. Moreover, it has been observed that oxidative stress regulates the expression of genes governing lipid and glucose metabolism through activation or inhibition of intracellular sensors. Diet constituents can modulate redox reactions and the oxidative stress extent, thus also acting on nuclear gene expression. As a consequence of the food-gene interaction, metabolic syndrome patients may express different disease features and extents according to the different pathways activated by oxidative stress-modulated effectors. This view could also explain family differences and interethnic variations in determining risk factor appearance. This review mechanistically focused on oxidative stress events leading to individual disease factor appearance in metabolic syndrome patients and their setting for a more helpful clinical approach.

Original languageEnglish (US)
Pages (from-to)491-504
Number of pages14
JournalJournal of Nutritional Biochemistry
Issue number8
StatePublished - Aug 2008


  • Diabetes
  • Endothelial dysfunction
  • HFE
  • Insulin resistance
  • Nonalcoholic fatty liver disease
  • Reactive oxygen species
  • Visceral obesity
  • hemochromatosis gene

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism
  • Biochemistry
  • Molecular Biology
  • Nutrition and Dietetics
  • Clinical Biochemistry


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