Effects of Concurrent Training on Oxidative Stress and Insulin Resistance in Obese Individuals
Evidence for a relationship between oxidative stress and insulin action in mass (LBM), waist to hip ratio, and arterial blood pressure volunteered for the study. Public Health Oxidative Stress Internal Medicine Human Physiology Metabolic Disease. These keywords were added by machine and not by the authors. Anthropometric parameters, IR, and oxidative stress were analyzed before and Also, it was observed that concurrent training, depending on the frequency, . relationship between oxidative stress and insulin action [36–38].
In humans, RBP4 levels have been shown to be elevated in several groups of insulin-resistant subjects Graham et al. It has been suggested that increased serum RBP4 levels might contribute to insulin resistance by impairing insulin-stimulated glucose uptake in muscles and elevating hepatic glucose production, although the mechanism is not fully clear Yang et al.
Other adipocyte factors Cortisol is another endocrine factor produced by adipose tissue.Is Insulin Really a Response to Carbohydrate or Just a Gauge of Energy Status? - MWM 2.23
Elevated glucocorticoid levels cause insulin resistance and T2DM Seckl et al. Circulating glucocorticoid levels are near normal in obesity Hautanen et al. Indeed, liver-specific antagonism of glucocorticoid action reduces hepatic glucose output and improves glucose control in animal models of obesity-associated insulin resistance Jacobson et al. The increased delivery of FA and cortisol, as well as adipokines Bujalska et al.
Other molecular differences between visceral and peripheral fat may also contribute to insulin resistance associated with visceral adiposity Gesta et al. Previous Section Next Section Inflammatory mechanisms Systemic chronic inflammation has been proposed to have an important role in the pathogenesis of obesity-related insulin resistance Hotamisligil et al.
Unequivocal experimental, epidemiological, and clinical evidence produced during the past decade causally links inflammation to the development of insulin resistance and T2DM Dandona et al. Activation of inflammatory pathways in hepatocytes is sufficient to cause both local Arkan et al. Furthermore, obesity is characterized by macrophage accumulation in white adipose tissue, which has added another dimension to our understanding of the development of adipose tissue inflammation in obesity Weisberg et al.
Adipose tissue macrophages ATMs are likely to contribute to the production of several of the adipokines discussed earlier. A causative role of ATMs in obesity-associated insulin resistance has been recently supported by studies showing that inhibition of macrophage recruitment in obesity ameliorates the insulin resistance seen in animal models Fig.
Several signaling pathways link the endocrine and inflammatory mechanisms of insulin resistance Fig.
In both genetic and dietary animal models of obesity, JNK1 activity is increased in the liver, muscle, and adipose tissue, and loss of JNK1 prevents insulin resistance Hirosumi et al. Modulation of hepatic JNK1 in adult animals also produces systemic effects on glucose metabolism, which underscores the importance of this pathway in the liver Nakatani et al.
This might trigger a vicious loop of heightened inflammatory responses that feed into the negative regulation of insulin signaling discussed earlier Fig. Another class of inflammatory mediators contributing to obesity-induced insulin resistance are SOCS proteins, which constitute a negative feedback pathway in cytokine signaling Fig.
Interestingly, recent studies reported increases in SOCS-3 in obese rodents, and reduction in SOCS-3 expression results in resistance to high-fat-diet-induced obesity and insulin resistance Howard et al.
Finally, recent studies have provided more clues to the interrelationship between obesity, inflammation, stress, and insulin resistance Matsuzawa et al. Moreover, Matsuzawa et al. Previous Section Next Section Neural mechanisms A key role for the brain in glucose homeostasis was suggested more than a century ago Bernard Recent evidence now indicates that the brain processes information from adiposity signals such as insulin and leptin, which circulate in proportion to body fat mass, and integrates this input with signals from nutrients such as FAs Burcelin et al.
In response, the brain sends signals to control feeding behavior and substrate metabolism in ways that promote homeostasis of both energy stores and fuel metabolism Fig. Both leptin and insulin play a role in the central control of peripheral glucose metabolism.
The insulin resistance of lipodystrophic and leptin-deficient mice is ameliorated by central leptin administration at doses that are much lower than the systemic doses needed to achieve the same phenotype Ebihara et al. Moreover, inhibition of hypothalamic insulin receptor function results in hepatic insulin resistance and impaired inhibition of hepatic glucose output Obici et al. Peripheral and brain insulin receptors are both required for normal insulin action Okamoto et al.
Intriguingly, leptin and insulin both induce the expression of SOCS-3, and sensitivity to both insulin and leptin is augmented in mice with reduced neuronal expression of SOCS-3 Mori et al. Obesity-associated nutrients such as FAs also have central effects on insulin action. Central infusion of oleic acid potently increases hepatic insulin sensitivity in rats Obici et al. The rate constant of the reaction when ferrous ions are reacted as 1.
The iron ions stimulate lipid peroxidation by the lipid degradation reactions from the present of abundant hydroperoxide. Iron or copper in a biological system attach to biological molecules at the specific location of OH radicals formation to cause lipid, protein and DNA damage. On lipid membrane, the propagation step of lipid peroxidation reactions does not proceedes further until the reaction reach the protein portion. Thus, lipid peroxidation in vivo causes proteins membrane damage[ 8081 ].
This damage has more biologically important than those lipids membrane damage. Cells also contain mechanisms for recognizing and removing oxidative modified proteins[ 8081 ]. Oxidative stress was defines as the increasing ROS production, vary in intensities, the different cellular locations and may be occurred either acutely or chronically[ 82 ].
Oxidative damage to macromolecules including carbohydrates, proteins, lipids and DNA typically viewed as increased ROS induced cellular damage to cause the irreversible macromolecules modifications. Therefore, the by-products of these oxidative modified biomolecules are used as oxidative stress biomarkers in vivo and in vitro.
Many research studies demonstrated the association of oxidative stress and the pathogenesis of insulin resistance via insulin signals inhibition and adipocytokines dysregulation[ 89 ].
Assaying lipid peroxidation The lipid peroxidation contributes to the pathogenesis of atherosclerosis. It is occurred in the blood vessel walls and does not occur from low density lipoproteins LDL in circulation[ 8788 ].
LDL can enter to the blood vessel walls. Therefore, this circulating LDL peroxidation is a potentially useful biomarker of lipid peroxidation in circulation. Indeed, this assay is used for the demonstration of in vivo antioxidants inhibit the effects of lipid peroxidation[ 8990 ]. Serum MDA levels have been used as the lipid peroxidation biomarker and indicator of free radical damage[ 3783]. MDA, the three-carbon dialdehyde, can exist in many forms in the aqueous circulation.
This method was used the reaction of MDA with TBA and heated under acidic conditions but the TBA can react with many chemical species such as proteins, phospholipids, aldehydes, amino acid and nucleic acids.
One MDA molecule reacts with TBA two molecules to form a stable pink to red chromophore that absorbs maximally at nm[ ] or fluorescence detection. This chromophore is termed thiobarbituric acid reacting substances. Isoprostanes The most valuable of lipid peroxidation biomarker in the biological system is the isoprostanes, elevated from the PUFA peroxidation[ - ]. Isoprostanes identified as free form and the most are esterified to lipids in circulation. Isoprostanes can be analyzed by mass spectrometry techniques, so that can easily be detected in human body fluids[,].
Isoprostanes appear to turn over rapidly in metabolized and excreted. Isoprostanes and their metabolites detection in urine may be the useful biomarker for lipid peroxidation[ ]. Isoprostanes assay have focused on the F2-isoprostanes measurement, which elevate from the arachidonic acid peroxidation[ ].
Elevation of F2-isoprostanes levels have been shown in conditions of the cardiovascular disease, diabetes development, cigarette smoking[, ], hyperhomocysteinaemia[ ] and hypercholesterolaemia. F2-isoprostane levels have also been shown to decrease by antioxidants supplementation both in animal models and humans subjects[ - ].
Oxidative stress in metabolic syndrome The components of metabolic syndrome consist with abdominal obesity, dyslipidemia, hypertension and diabetes. It is the major modern lifestyle complication cause from physical inactivity and overeating and associated with the increased risk of cardiovascular diseases, hypertension and T2DM that summarized in Figure 4.
Free fatty acid; MetS: Over nutrition and oxidative stress: In over nutrition, the excessive glucose occur and a large amount of glucose is oxidized in the glycolysis and TCA cycle to increase NADH and FADH2 generation in electron transport chain of mitochondrial and increased superoxide generation[ ].
Thus, over accumulated fat result in the increased fatty acids oxidation and lead to activate NADPH oxidase in local or remotely cells to cause ROS over production in over nutrition or obesity Figure 4.
Conversely, calorie restriction may be associated with normal physiological system[ ] and may involve in normal cellular redox state[ ]. In aged animals models treated with antioxidant agents or hypocaloric diets led to ameliorate in oxidative stress status and tissue function.
Treatment with resveratrol, a polyphenol reduced atherosclerosis and diabetes development[ ]. These studies demonstrate that nutrition is associated with increased or decreased redox status and over nutrition result to increase oxidative stress to contribute pathogenesis of atherosclerosis, cancer and other diseases. Oxidative stress in adipose tissue: Increased fat accumulation in human has been associated with oxidative stress biomarkers[ ]. Similarly, obese mice were significantly higher oxidative stress levels in circulation[ 8 ].
Moreover, lipid peroxidation and H2O2 levels were increased in adipose tissue[ 8 ]. These mean that adipose tissue may the major source of ROS production and can be released to the circulation potentially affecting various distance organs functions and damage Figure 4.
Mechanisms of obesity-associated insulin resistance: many choices on the menu
Increased NADPH oxidase expression in adipose tissue associated with increased oxidative stress levels. Increased mRNA expression was found in adipose tissue of obese mice[ 8 ]. Moreover, obese mice ameliorated hyperinsulinemia, hypertriglyceridemia, hyperglycemia and hepatic steatosis by supplementation with apocynin[ 8 ].
Adipose tissue tries to increase antioxidant enzymes levels to against ROS over production. However, these antioxidant enzymes activity and expression are decreased in adipose tissue[ 8- ].
- Oxidative stress and insulin action: is there a relationship?
- Mechanisms of obesity-associated insulin resistance: many choices on the menu
- Oxidative Medicine and Cellular Longevity
Then, increased ROS-production enzymes and decreased antioxidant enzymes may cause oxidative stress in obese and metabolic syndrome. Oxidative stress and salt-sensitive hypertension: As in mention above, ROS levels are increased in obesity and can be ameliorated by weight loss[ 7 ]. Obese rats induced by refined sugar or high fat diet leading to ROS overproduction and increase oxidative stress[ 6].
Many research evidences suggest that metabolic syndrome was associated with the salt-sensitive hypertension. ROS play the roles as mechanical link of metabolic syndrome and salt-sensitive hypertension, which itself leads to ROS overproduction[ - ].
Salt restriction in hypertensive obesity was more effective reduction in blood pressure than in hypertensive non-obesity patients, and weight loss in obesity and salt sensitive hypertensive patients caused the successful of blood pressure reduction[ ]. Salt-sensitive hypertensive patients were significantly more prevalent in metabolic syndrome patients than without metabolic syndrome[ ].
Interestingly, infused Ang II-rats disturbed sodium balance to cause ROS overproduction in salt-sensitive rats[ - ]. Moreover, in salt-sensitive hypertensive patients are also increased 8-isoprostane levels[ ]. Thus, ROS may the underling pathogenesis of diseases in metabolic syndrome, obese and non-obese intake excessive salt as the salt-sensitive hypertensive patients.
In high-renin patients non-modulating salt sensitive hypertension had elevated the homeostasis model assessment of insulin resistance HOMA-IR levels[ ]. Insalt-sensitive hypertensive non-obesity patients had significantly lower insulin sensitivity than in non-salt-sensitive hypertensive patients[ ]. Increased renal ROS overproduction may increase the salt sensitive hypertension[ ].
Then, increased renal oxidative stress may contribute to cause salt-sensitive hypertension development. Moreover, ROS overproduction in vascular endothelial cells suppresses the NO-dependent vasodilation[ ] and may play the role in the salt-sensitive hypertension development.
Oxidative stress in type 2 diabetes Many research studies demonstrated that T2DM patients have increased ROS production-induced higher oxidative damage in the circulation and also have reduced antioxidant defenses mechanisms[ - ]. Elevated free fatty acids, leptin and other circulating factors in T2DM patients may also contribute to cause ROS overproduction.
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Oxidized low density lipoprotein; FFA: Free fatty acids; AGEs: Advanced glycation end-products; VSMC: Vascular smooth muscle cells; ROS: NADH overproduction can cause the higher proton gradient production in mitochondria. These electrons are transferred to oxygen to produce higher superoxide[ ]. The NADH dehydrogenase of the complex I ubiquinone oxidoreductase and complex III cytochrome c reductase are the two main site of superoxide production via the electron transport chain[ ].
The polyol pathway Oxidative stress increased in circulation of T2DM patients from the polyol pathway. ROS was generated by two enzymes: Sorbitol production is a minor reaction in normal physiological conditions. In the condition of sorbitol overproduction, the availability of NADPH is reduced this reflect to reduce glutathione regeneration and NOS synthase activity to cause increased oxidative stress[ ]; and 2 Sorbitol dehydrogenase in the second step oxidizes sorbitol to fructose concomitant with NADH overproduction.
Non-enzymatic glycation Glycation end-product is the binding of ketone or aldehyde groups of glucose with the free amino groups of proteins leading Schiff bases formation without enzymes, then to form the Amadori product and rearrangements of the structure to the irreversible AGEs in the final.