The role of mitochondrial oxidative stress in the metabolic alterations in diet‐induced obesity in rats

Abstract

The impact of the mitochondria‐targeted antioxidant MitoQ was evaluated in the metabolic alterations and the adipose tissue remodeling associated with obesity. Male Wistar rats were fed either a high‐fat diet (HFD; 35% fat) or a standard diet (3.5% fat) for 7 wk and treated with MitoQ (200 μM). A proteomic analysis of visceral adipose tissue from patients with obesity and patients without obesity was performed. MitoQ partially prevented the increase in body weight, adiposity, homeostasis model assessment index, and adipose tissue remodeling in HFD rats. It also ameliorated protein level changes of factors involved in insulin signaling observed in adipose tissue of obese rats: reductions in adiponectin and glucose transporter 4 (GLUT 4) and increases in dipeptidylpeptidase 4, suppressor of cytokine signaling 3 (SOCS3), and insulin receptor substrate 1 phosphorylation. MitoQ prevented down‐regulation of adiponectin and GLUT 4 and increases in SOCS3 levels in a TNF‐α‐induced insulin‐resistant 3T3‐L1 adipocyte model. MitoQ also ameliorated alterations in mitochondrial proteins observed in obese rats: increases in cyclophylin F and carnitine palmitoyl transferase 1A and reductions in mitofusin1, peroxiredoxin 4, and fumarate hydratase. The proteomic analysis of the visceral adipose tissue from patients with obesity show alterations in mitochondrial proteins similar to those observed in obese rats. Therefore, the data show the beneficial effect of MitoQ in the metabolic dysfunction induced by obesity.—Marín‐Royo, G., Rodríguez, C., Le Pape, A., Jurado‐Lopez, R., Luaces, M., Antequera, A., Martinez‐Gonzalez, J., Souza‐Neto, F. V., Nieto, M. L., Martínez‐Martínez, E., Cachofeiro, V. The role of mitochondrial oxidative stress in the metabolic alterations in diet‐induced obesity in rats. FASEB J. 33, 12060‐12072 (2019). http://www.fasebj.org

The Crosstalk between Cardiac Lipotoxicity and Mitochondrial Oxidative Stress in the Cardiac Alterations in Diet-Induced Obesity in Rats

“…Animals fed an HFD showed an increase in body weight and adiposity index after seven weeks of HFD intake when compared to control rats [12]. Obese rats also showed an increase in relative heart weight, suggesting cardiac hypertrophy, cardiomyocyte area, and cardiac fibrosis, although no changes in cardiac function or blood pressure were observed (Table 1, Figure 1A,B).…”

“…Mitochondria are also the main source of reactive oxygen species (ROS), which can be exacerbated in different pathological conditions, including obesity [10,11]. Dysregulation of mitochondrial function in the context of obesity can participate not only in the cardiac consequences of obesity, but as well as in its metabolic ones, since the administration of a mitochondrial antioxidant was able to improve cardiac damage and improve insulin resistance in adipose tissue associated with obesity [10,[12][13][14]. Although the potential role of cardiolipotoxicity and mitochondrial oxidative stress in the cardiac damage associated with obesity is accepted, how these two mechanisms interact in this damage remains unclear.…”

PGC-1α, Inflammation, and Oxidative Stress: An Integrative View in Metabolism

“…Several studies have emphasized high ROS levels in diabetic patients and the role of ROS in cellular signaling alteration, which contributes to the development and complications of T2DM [184]. As previously mentioned, mitochondrial dysfunction is associated with T2DM, and this mitochondrial impairment may trigger oxidative stress [164]. Therefore, PGC-1α and oxidative stress are involved in T2DM.…”

“…To conclude, mitochondrial dysfunction is associated with obesity but not with glucose tolerance [163]. Interestingly, mitochondrial dysfunction may potentially exacerbate ROS production and can also diminish the availability of ATP, which is indispensable for the transcription of antioxidant and DNA-repair genes and, therefore, leads to oxidative stress [164]. Moreover, the genes encoding mitochondrial proteins reduce in obese mice without diabetes, which are upregulated after rosiglitazone treatment [165].…”

Potential Biomarkers for Feed Efficiency-Related Traits in Nelore Cattle Identified by Co-expression Network and Integrative Genomics Analyses

“…The PEDF is also described as a negative regulator of fat mass (Ma et al, 2018). The relationship between oxidative stress and fat mass was reported in a study with mice, where the increment in oxidative stress was related to obesity induced by diet (Marín-Royo et al, 2019).…”