Oxidative stress-induced risk factors associated with the metabolic syndrome: a unifying hypothesis.
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.
Grattagliano
Ignazio
I
Department of Internal Medicine and Public Medicine, University Medical School of Bari, Clinica Medica "A. Murri," 70124 Bari, Italy.
Palmieri
Vincenzo O
VO
Portincasa
Piero
P
Moschetta
Antonio
A
Palasciano
Giuseppe
G
D000818:Animals; D003920:Diabetes Mellitus; D004730:Endothelium, Vascular; D005234:Fatty Liver; D020022:Genetic Predisposition to Disease; D006801:Humans; D006943:Hyperglycemia; D006973:Hypertension; D007333:Insulin Resistance; D050152:Intra-Abdominal Fat; D050356:Lipid Metabolism; D024821:Metabolic Syndrome / Q000209:etiology*; D008954:Models, Biological; D009747:Nutritional Physiological Phenomena; D009765:Obesity; D010084:Oxidation-Reduction; D018384:Oxidative Stress; D012307:Risk Factors