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Recently, we demonstrated that the hypothalamic S1PR1/STAT3 axis plays a critical role in the control of food consumption and energy expenditure in rodents. Here, we found that reduction of hypothalamic S1PR1 expression occurs in an age-dependent manner, and was associated with defective thermogenic signaling and weight gain. To address the physiological relevance of these findings, we investigated the effects of chronic and acute exercise on the hypothalamic S1PR1/STAT3 axis. Chronic exercise increased S1PR1 expression and STAT3 phosphorylation in the hypothalamus, restoring the anorexigenic and thermogenic signals in middle-aged mice. Acutely, exercise increased sphingosine-1-phosphate (S1P) levels in the cerebrospinal fluid (CSF) of young rats, whereas the administration of CSF from exercised young rats into the hypothalamus of middle-aged rats at rest was sufficient to reduce the food intake. Finally, the intracerebroventricular (ICV) administration of S1PR1 activators, including the bioactive lipid molecule S1P, and pharmacological S1PR1 activator, SEW2871, induced a potent STAT3 phosphorylation and anorexigenic response in middle-aged rats. Overall, these results suggest that hypothalamic S1PR1 is important for the maintenance of energy balance and provide new insights into the mechanism by which exercise controls the anorexigenic and thermogenic signals in the central nervous system during the aging process.

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Inducible nitric oxide (iNOS)-mediated S-nitrosation of the metabolic signaling pathway has emerged as a post-translational modification that triggers insulin resistance in obesity and aging. However, the effects of S-nitrosation in controlling energy homeostasis are unknown. Thus, in the present study we aimed to evaluate the effects of S-nitrosation in insulin signaling pathway in the hypothalamus of rodents. Herein, we demonstrated that the intracerebroventricular infusion of the nitric oxide (NO) donor S-nitrosoglutathione (GSNO) promoted hypothalamic insulin signaling resistance and replicated the food intake pattern of obese individuals. Indeed, obesity induced S-nitrosation of hypothalamic IR and Akt, whereas inhibition of iNOS or S-nitrosation of insulin signaling pathway protected against hypothalamic insulin resistance and normalized energy homeostasis. Overall, these findings indicated that S-nitrosation of insulin signaling pathway is required to sustain hypothalamic insulin resistance in obesity.

Hypothalamic interleukin-6 (IL6) exerts a broad metabolic control. Here, we demonstrated that IL6 activates the ERK1/2 pathway in the ventromedial hypothalamus (VMH), stimulating AMPK/ACC signaling and fatty acid oxidation in mouse skeletal muscle. Bioinformatics analysis revealed that the hypothalamic IL6/ERK1/2 axis is closely associated with fatty acid oxidation– and mitochondrial-related genes in the skeletal muscle of isogenic BXD mouse strains and humans. We showed that the hypothalamic IL6/ERK1/2 pathway requires the α2-adrenergic pathway to modify fatty acid skeletal muscle metabolism. To address the physiological relevance of these findings, we demonstrated that this neuromuscular circuit is required to underpin AMPK/ACC signaling activation and fatty acid oxidation after exercise. Last, the selective down-regulation of IL6 receptor in VMH abolished the effects of exercise to sustain AMPK and ACC phosphorylation and fatty acid oxidation in the muscle after exercise. Together, these data demonstrated that the IL6/ERK axis in VMH controls fatty acid metabolism in the skeletal muscle.

Background: Multicomponent training has considerable adherence among older populations, but there is a lack of literature on the benefits of this training on older people’s posture. Literature also lacks stretching protocols that work the body in an integrated/unified way and respect the principle of individuality in exercise training. We evaluated the effect of a multicomponent training protocol combined or not with flexibility training in improving the posture and quality of movement in physically inactive older women, according to a score lower than 9.11 in the Modified Baecke Questionnaire for the Elderly (MBQE). Methods: 142 participants were evaluated and randomized in three training groups: multicomponent training (MT = 52), multicomponent and flexibility training (MFT = 43), and a control group (CG = 47). We evaluated joint amplitude using goniometry, flexibility with sit and reach and hands behind the back tests, quality of movement with the functional movement screen, and posture using biophotogammetry. Results: The MFT group had 15 parameters—flexibility and posture—with a very large effect size (ES > 1.30) and nine with average ES (0.50–0.79). MT presented two variables with large ES (0.80–1.25) and seven with average ES. CG presented three variables with high ES and five with average ES. Both interventions improved the quality of movement. Conclusions: These results demonstrate that 14 weeks of multicomponent and flexibility training in a group intervention can improve flexibility and posture levels in physically inactive older women.

The main objective of this study was to examine the effect of continuous aerobic training (CAT) in hypertensive, obese people. Seven patients of average age (45.3±3.9 years), height (1.63±0.1 m), body weight (89.09±22.0 kg), and body mass index (33.44±8.6 kg/m2) were subjected to the training. CAT was performed in thrice-weekly nonconsecutive sessions (90 min per week) with intervals of 48 hr between each session. The training sessions entailed 30 min of walking at an intensity of 70%–80% of the maximum heart rate (MHR) on a treadmill over a period of eight weeks, giving a total of 24 sessions. Through correlation analyses, we found significant improvement in the systolic pressure (R=0.5675, P=0.0253) and diastolic pressure (R=0.7083, P=0.0088) when the last session was compared to the first session of training. We found no differences in the diastolic pressure and systolic pressure before, during and after 15 min of the protocol exercise. The program showed a large effect size (ES) for systolic pressure (ES=0.85) and a small ES for diastolic pressure (ES=0.33). We found no differences in the blood pressure (BP) and heart rate (HR) during and after the training of obese hypertensive humans, but we found a positively significant correlation between HR and BP in the last session and a large ES, suggesting that this protocol exercise might have significance effect in the long term.

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