FOXO1 is downregulated in obese mice subjected to short-term strength training.

Obesity is a worldwide health problem and is directly associated with insulin resistance and type 2 diabetes. The liver is an important organ for the control of healthy glycemic levels, since insulin resistance in this organ reduces phosphorylation of forkhead box protein 1 (FOXO1) protein, leading to higher hepatic glucose production (HGP) and fasting hyperglycemia. Aerobic physical training is known as an important strategy in increasing the insulin action in the liver by increasing FOXO1 phosphorylation and reducing gluconeogenesis. However, little is known about the effects of strength training in this context. This study aimed to investigate the effects of short-term strength training on hepatic insulin sensitivity and glycogen synthase kinase-3ß (GSK3ß) and FOXO1 phosphorylation in obese (OB) mice. To achieve this goal, OB Swiss mice performed the strength training protocol (one daily session for 15 days). Short-term strength training increased the phosphorylation of protein kinase B and GSK3ß in the liver after insulin stimulus and improved the control of HGP during the pyruvate tolerance test. On the other hand, sedentary OB animals reduced FOXO1 phosphorylation and increased the levels of nuclear FOXO1 in the liver, increasing the phosphoenolpyruvate carboxykinase (PEPCK) and glucose-6-phosphatase (G6Pase) content. The bioinformatics analysis also showed positive correlations between hepatic FOXO1 levels and gluconeogenic genes, reinforcing our findings. However, strength-trained animals reverted to this scenario, regardless of body adiposity changes. In conclusion, short-term strength training is an efficient strategy to enhance the insulin action in the liver of OB mice, contributing to glycemic control by reducing the activity of hepatic FOXO1 and lowering PEPCK and G6Pase contents.

Neurotoxicity associated with chronic exposure to dichlorophenoxyacetic acid (2,4-D) - a simulation of environmental exposure in adult rats.

The herbicide 2,4-dichlorophenoxyacetic acid (2,4-D) is the second most widely used herbicide in the world. The objective of this study was to evaluate the neurotoxic effects and the possible role of the dysregulation of apoptosis in the genesis of brain damage in chronic exposure to 2,4-D in rats. Eighty adult male rats were distributed into eight groups (n = 10) and exposed orally (contaminated feed) and via inhalation, with two groups exposed to distilled water (control) and six to 2,4-D in three distinct concentrations. They were exposed for 6 months. A neurobehavioral assessment was performed, and the brain was collected for histopathology and immunohistochemistry. The animals in the control groups showed greater motility in the open-field test and a greater number of entries in the elevated-plus-maze test than those exposed to 2,4-D (p < 0.05). Neuronal necrosis was more incident in animals exposed to 2,4-D (p < 0.05). There was a negative correlation between the expression of BAX and the measurement of the cerebral cortex thickness (r = -0.713; p = 0.047). Regardless of the route of exposure, 2,4-D led to a deficit in neurobehavioral tests and decreased thickness of the cerebral cortex associated with increased expression of the pro-apoptotic protein BAX.

Moderate, but Not Excessive, Training Attenuates Autophagy Machinery in Metabolic Tissues.

The protective effects of chronic moderate exercise-mediated autophagy include the prevention and treatment of several diseases and the extension of lifespan. In addition, physical exercise may impair cellular structures, requiring the action of the autophagy mechanism for clearance and renovation of damaged cellular components. For the first time, we investigated the adaptations on basal autophagy flux in vivo in mice's liver, heart, and skeletal muscle tissues submitted to four different chronic exercise models: endurance, resistance, concurrent, and overtraining. Measuring the autophagy flux in vivo is crucial to access the functionality of the autophagy pathway since changes in this pathway can occur in more than five steps. Moreover, the responses of metabolic, performance, and functional parameters, as well as genes and proteins related to the autophagy pathway, were addressed. In summary, the regular exercise models exhibited normal/enhanced adaptations with reduced autophagy-related proteins in all tissues. On the other hand, the overtrained group presented higher expression of Sqstm1 and Bnip3 with negative morphological and physical performance adaptations for the liver and heart, respectively. The groups showed different adaptions in autophagy flux in skeletal muscle, suggesting the activation or inhibition of basal autophagy may not always be related to improvement or impairment of performance.