Significance: Since the metabolic syndrome (MS) and pathologies associated with/resulting from metabolic dysregulations became a worldwide spreading and growing problem, the mechanisms mediating the according cellular changes got into a focus of interest. The ubiquitin-proteasomal system (UPS) is the main regulator of both the functional and dysfunctional protein pool of (not only) mammalian cells-thus, it is obvious that an impact on this system may also affect cellular functionality that directly depends on permanent regulation/adaption of the cell's proteostasis. However, the according research is still at the beginning. Recent Advances: It was also recently shown that maintaining a highly functional UPS positively correlates with increased health or even life span, thus modulation or restoration of UPS function may be an effective approach alleviating or even preventing MS detrimental consequences.
Critical issues: Even if many consequences of metabolic dysregulation such as a slight but chronic redox shift to a more oxidative state (i.e., a low-grade systemic inflammation that increases reactive oxygen species formation, lipid peroxidation, protein oxidation, formation of advanced glycation end products, glycosylation, S-glutathionylation, redox shifts, endoplasmic reticulum stress, unfolded protein response, expression of transcription factors, and release of cytokines) are already known to affect the highly redox-regulated UPS, experimental data about UPS changes that are directly mediated by glucotoxic and/or lipotoxic stress are still rarely published.
Future directions: It may be taken into account that many MS-related pathologic changes result from UPS dysfunction or dysregulation. In this review, the main interface between MS effects and their impact on the UPS are highlighted since they may direct to new therapeutic approaches. Antioxid. Redox Signal. 25, 902-917.
Keywords: ROS; inflammation; metabolism; nutrition; proteasome; redox.