Ricardo Augusto Leoni De Sousa

Insulin resistance (IR) is a pathological condition in which peripheral tissues and the brain fail to respond effectively to circulating insulin, contributing to metabolic disorders and cognitive decline. Adipose distribution, and hormonal regulation modulate IR, resulting in distinct molecular and metabolic profiles between men and women. Physical exercise is a potent intervention for improving insulin sensitivity, impacting both peripheral and central mechanisms. At the molecular level, exercise enhances insulin signaling, glucose uptake, and mitochondrial function in skeletal muscle, liver, and adipose tissue. In the brain, exercise-induced factors such as PGC-1α and irisin mediate neuroplasticity, neuroprotection, and energy metabolism, contributing to improved cognitive function and reduced risk of neurodegenerative disease. Physical exercise modulates lipid intermediates, inflammatory markers, and transcriptional networks that contribute to IR, highlighting its systemic and tissue-specific effects. Understanding these mechanisms is essential for the development of precision exercise prescriptions tailored to individual metabolic and neurological profiles. This review synthesizes current evidence on the molecular mechanisms underlying peripheral and brain IR and examines how aerobic, resistance, and high-intensity interval training influence these pathways. By integrating molecular, physiological, and behavioral perspectives, this work underscores the critical role of physical exercise in mitigating IR and promoting metabolic and cognitive health.

SUMMARY OBJECTIVE: The aim of this study was to evaluate the association between lower limb strength and symptoms of anxiety and depression in communitydwelling older adults. METHODS: This cross-sectional study included 99 community-dwelling older adults (69.5±6.6 years; 81.8% women) assessed between 2021 and 2023 in Minas Gerais, Brazil. Inclusion criteria were age ≥60 years, independent mobility, and medical clearance. Participants were excluded if they had uncontrolled chronic or cardiovascular diseases, a history of stroke, unmanaged neurodegenerative disorders, active psychiatric comorbidities that could interfere with psychological assessments, or musculoskeletal injuries preventing safe participation in testing. Anxiety and depressive symptoms were assessed using the Geriatric Anxiety Inventory and Geriatric Depression Scale. Lower limb strength was measured using the 30-Second Chair Stand test and classified according to age- and sex-specific normative values. RESULTS: Participants with below-average lower limb strength had higher odds of anxiety symptoms (OR 10.90; 95%CI 1.97–60.33; p=0.006). Lower limb strength was also associated with depressive symptoms, although with a smaller effect size (OR 3.96; 95%CI 1.06–14.74; p=0.040). Age was positively associated with anxiety (p=0.019), while no significant associations were observed for sex. CONCLUSION: The 30-Second Chair Stand test may have potential as a complementary screening indicator to identify older adults at elevated psychosocial risk.

Exercise increases peroxisome proliferator-activated receptor-gamma coactivator 1-alpha (PGC-1α) expression, which in turn causes the fibronectin type III domain containing 5 (FNDC5) protein to be produced. This protein is then cleaved, primarily in skeletal muscle fibers, to produce irisin. When the mature FNDC5 is cleaved by proteases, Irisin - which is the fibronectin III domain without the signal sequence - is released. Resistance, aerobic, and high-intensity interval training (HIIT) are recognized as forms of physical exercise that raise irisin levels, and insulin receptor phosphorylation in tyrosine residues, favoring an increase in the activity of the insulin-dependent pathway (PI3K pathway) and assisting in the fight against insulin resistance, inflammation, and cognitive decline. Irisin may represent a promising option for the therapeutic targeting in several brain-related pathological conditions, like Alzheimer’s disease (AD), Parkinson’s disease (PD), epilepsy, type 2 diabetes, and obesity. Exercise protocols are healthy and inexpensive interventions that can help find cellular and molecular changes in several brain-related pathological conditions. Here, it was reviewed what is known about exercise-produced irisin studies involving AD, PD, epilepsy, type 2 diabetes, and obesity.

This study aimed to compare the effects of High-Intensity Interval Training (HIIT) performed in a single session(1xHIIT) versus three daily sessions (3xHIIT) on fitness level and behavior of aged rats. Eighteen-month-old Wistar rats were assigned to Untrained (UN), 1xHIIT, or 3xHIIT (n = 12/group). Both groups, 1xHIIT and 3xHIIT, performed 15 min of a treadmill running HIIT protocol during 8 weeks. 1xHIIT protocol consisted of a single daily session of 15 min, while the 3xHIIT performed three daily sessions of 5 min with a 4 h interval between the sessions. Morris Water Maze (MWM) task was used to evaluate spatial learning and memory. Splash test, Forced Swim test, and Elevated Plus Maze task (EPM) were used to evaluate anhedonic, depressive-like, and anxious behaviors, respectively. Rats were euthanized, and the hippocampus was harvested for western blot analyses (CaMKII and BDNF). Both HIIT protocols improved VO₂max and spatial memory. Notably, only the 3xHIIT protocol attenuated anxious and depressive-like behaviors. Western blot analyses of the hippocampus revealed that both HIIT protocols increased BDNF levels. BDNF levels were higher in the 3xHIIT when compared with 1xHIIT group, and we observed increasement of the CamKII levels just in the 3x HIIT group. Therefore, this study provides evidence indicating that accumulated HIIT sessions is more effective than traditional daily HIIT sessions in improving fitness level, cognitive function, memory, inhibiting the development of mood disorders, and enhancing BDNF and CaMKII levels in the hippocampus of aged rats.