Aging is a process characterized by tissue degeneration, increased susceptibility to chronic degenerative diseases, infections, and the appearance of neoplasms, which leads to disability and a reduction in the length and quality of life. This phenomenon is the result of the convergence of multiple processes, including mitochondrial dysfunction, fibrosis, inflammation, dysregulation of cell death processes, and immunosenescence. These processes have as their point of convergence an increase in the production of ROS. Avocado oil (Persea americana Mill.) contains a diverse array of bioactive compounds, including oleic acid, phytosterols, chlorophylls, xanthones, xanthines, and carotenoids. These bioactive compounds have the capacity to modulate the excessive production of ROS, thereby reducing the progression of age-related diseases and extending lifespan in experimental models of aging. In addition, several studies have demonstrated the efficacy of avocado oil in mitigating age-related diseases, including hypertension; insulin resistance; diabetes; non-alcoholic liver disease; and degenerative processes such as hearing loss, cognitive decline, neurodegeneration, and impaired wound healing. In light of these findings, it is hypothesized that avocado oil is a promising agent capable of promoting healthspan in later stages of life owing to its direct antioxidant actions and the activation of pathways that enhance endogenous antioxidant levels.

High-fat and high-carbohydrate (HF-HC) diets induce metabolic syndrome via mitochondrial dysfunction and oxidative stress. We have previously shown that this may be prevented by avocado oil, a source of bioactive molecules with antioxidant properties. However, it is unknown if these effects are mediated by the unsaponifiable fraction of avocado oil (UFAO). Thus, we tested if this fraction improves glucose metabolism, bioenergetics and oxidative stress in mitochondria from the kidney and liver of rats fed an HF-HC diet. We found that 12 weeks of an HF-HC diet impaired glucose utilization and increased insulin resistance, which was prevented by UFAO administration. The HF-HC diet decreased respiration, membrane potential and electron transport chain (ETC) function in liver and kidney mitochondria. These mitochondrial dysfunctions were prevented by UFAO intake. Unexpectedly, UFAO increased ROS levels in the mitochondria of control animals and did not decrease them in rats with an HF-HC diet; however, UFAO protects liver and kidney mitochondria from iron-induced oxidative stress. These findings suggest that impairments in glucose metabolism and mitochondrial function by an HF-HC diet may be prevented by UFAO, without decreasing ROS generation but protecting mitochondria from oxidative damage.

Obesity induces metabolic and functional alterations in skeletal muscle, particularly at the mitochondrial level, contributing to insulin resistance, oxidative stress, and reduced contractile capacity. This study evaluated the effects of moderate-intensity exercise, diazoxide, an activator of mitochondrial ATP-sensitive potassium (mitoK_ATP) channels, and their combination on mitochondrial bioenergetics in rats with high-fat diet-induced obesity over eight weeks. Eight experimental groups were used (n = 6 per group), with eight weeks of exercise and 14 days of diazoxide administration. Morphometric, biochemical, and functional parameters of mitochondria isolated from skeletal muscle were analyzed. Obesity was associated with significant increases in body weight, visceral adiposity, plasma glucose, and triglyceride levels, along with impaired mitochondrial respiration, increased mitochondrial swelling, reduced electron transport chain complex activity, increased oxidant-associated fluorescence, and decreased activity of superoxide dismutase (SOD) and glutathione peroxidase (GPx). In obese rats, exercise, diazoxide, and their combination were associated with favorable changes in redox-related parameters compared to the untreated obese group. Significant improvements were also observed in selected parameters of mitochondrial function, although responses varied among the interventions. Conversely, changes in certain morphometric and biochemical parameters, such as the Lee index and glucose levels, primarily reflected numerical trends toward control values. Overall, these findings suggest that exercise and diazoxide, individually or in combination, may attenuate selected mitochondrial alterations associated with obesity in this experimental animal model.