Excessive high caloric intake from either a high-carbohydrate or high-fat diet will cause more substrates to enter into mitochondrial respiration [44]. Subsequently, the number of electrons donated to the electron transport chain may increase [45]. Upon reaching a threshold voltage, extra electrons might back up at complex III with further donations to molecular oxygen, which produces high levels of superoxide [45].
Intriguingly, extremely high amounts of carbohydrates may lead to the reduction of insulin binding and the downregulated transcription of insulin receptor expression in the skeletal muscle [46]. High insulin and glucose levels may decrease insulin binding to the insulin receptor in adipocytes [47], negatively affecting Akt activity. The accumulation of ROS/RNS or a reduction of antioxidant capacity due to increased carbohydrate metabolism in insulin target tissues may change the phosphorylation status of these signaling pathways, subsequently resulting in deactivation. Indeed, exposure to hydrogen peroxide (H2O2) promotes a significant loss in distal and proximal insulin signaling and decreased glucose transport in muscles and adipocytes in vitro [48].
Substantial evidence has suggested that SFAs can boost proinflammatory signaling. The lengths of SFA chains can produce different physiological responses [84, 85], but many mechanisms are still debated. Long-chain SFAs including palmitate and myristate acids are typically known for their harmful effects against endothelial cells, which can induce apoptosis through the induction of NF-κB in human coronary artery endothelial cells (HCAECs) [86, 87]. Harvey et al. [86] showed that long-chain SFAs can promote proinflammatory endothelial cell phenotypes through the incorporation into endothelial cell lipids. Conversely, short- and medium-chain SFAs do not incorporate or contribute to lipotoxicity. Particularly, stearic acid stimulates the upregulation of ICAM-1 human aortic endothelial cells (HAECs) via an NF-κB dependent manner [86].
More recently, proteins have been found to suffer oxidative and nitrosative reactions during the digestion (defined above as “luminal oxidative stress”) and such reactions are considerably severe at particular locations (for example, stomach) under specific physiopathological conditions (for example, infection by Helicobacter pylori) (Van Hecke, Van Camp, & De Smet, 2017). Though the limitations of in vitro model systems are recognized, mechanistic studies that aimed to simulate the pro-oxidative environments occurred during food digestion have recently been carried out. Oueslati, de La Pomélie, Santé-Lhoutellier, and Gatellier (2016) observed the formation of hydroxyl and superoxide radicals during digestion of pork proteins in the presence of iron and established a connection between the extent of protein oxidation and the decreased digestibility of oxidized proteins. To similar conclusions came Rysman, Van Hecke, Van Poucke, et al. (2016) who stated that protein carbonylation in pork and beef patties led to impaired proteolysis in the proximal gut. Luna and Estévez (2019) recently corroborated the connection between the severity of carbonylation in meat and dairy proteins exposed to Maillard α-dicarbonyls and impaired digestibility. The decreased digestibility of oxidized proteins may not only involve a considerable loss of nutritional value as reported by Ferreira, Morcuende, Madruga, Silva, and Estévez (2018) and de la Pomélie et al. (2018) as the fermentation of undigested proteins in distant portions of the gut leads to the formation of toxic compounds (Soladoye et al.,
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Pathogenesis of Dietary Protein Oxidation: Recent Advances
Oxidized peptides and amino acids, derived whether from dietary oxidative stress or in vivo oxidative stress, display assorted pathological mechanisms. Certain oxidized amino acids are misincorporated into de novo synthesized proteins potentially contributing to malfunction of enzymes and structural element, cell apoptosis, and disease (Gurer-Orhan et al., 2006). Oxidized amino acids, such as meta-tyrosine and 3,4-dihydroxyphenylalanine (l-DOPA), are attributed such pathological mechanism leading to dysfunctional proteins and toxicity (Dunlop, Main, & Rodgers, 2015). l-DOPA, in particular, substitute l-tyrosine residues in proteins causing misfolding, protein aggregation, and apoptosis (Chan, Dunlop, Rowe, Double, & Rodgers, 2012).