RESUMEN
High-fat diet consumption causes hypothalamic inflammation, dysregulating the leptin pathway, which, in turn, compromises the modulation of hypothalamic neuronal activities and predisposes obesity development. Intermittent fasting (IF) and exercise training (ET) have been demonstrated as efficient interventions to modulate hypothalamic inflammation and neuronal activity. However, no studies have evaluated whether combining these interventions could induce better results in reestablishing hypothalamic homeostasis disrupted by high-fat diet intake. The 8-week-old male C57BL/6 mice were randomly assigned into 2 groups: sedentary mice fed a standard diet (CT), and sedentary mice fed a high-fat diet (HF). After 8 weeks of an HF diet, part of the HF group (now 16 weeks old) was randomly subjected to different interventions for 6 weeks: HF-IF = HF diet mice submitted to IF; HF-T = HF diet mice submitted to ET; HF-IFT = HF diet mice submitted to IF and ET. All interventions decreased the body weight gain induced by high-fat diet intake, associated with reduced calorie consumption in week 14. Only the HF-IFT group presented improved serum insulin, leptin, resistin, and Tnf-alpha levels concomitantly with decreased hypothalamic inflammation. The HF-IFT group also demonstrated increased Pomc mRNA expression associated with enhanced pSTAT3 expression in the hypothalamic arcuate and ventromedial hypothalamic nuclei. Our data indicate that the beneficial effects of the combination of IF and ET on energy homeostasis are associated with increased leptin sensitivity in the hypothalamic arcuate nucleus and ventromedial hypothalamic nucleus, which is likely due to an improvement in hypothalamic inflammatory pathways in these nuclei.
Asunto(s)
Dieta Alta en Grasa , Leptina , Masculino , Ratones , Animales , Dieta Alta en Grasa/efectos adversos , Ayuno Intermitente , Grasas de la Dieta/farmacología , Ratones Endogámicos C57BL , Hipotálamo/metabolismo , Inflamación/metabolismoRESUMEN
Intermittent fasting (IF) is a popular intervention used to fight overweight/obesity. This condition is accompanied by hypothalamic inflammation, limiting the proper signaling of molecular pathways, with consequent dysregulation of food intake and energy homeostasis. This mini-review explored the therapeutic modulation potential of IF regarding the disruption of these molecular pathways. IF seems to modulate inflammatory pathways in the brain, which may also be correlated with the brain-microbiota axis, improving hypothalamic signaling of leptin and insulin, and inducing the autophagic pathway in hypothalamic neurons, contributing to weight loss in obesity. Evidence also suggests that when an IF protocol is performed without respecting the circadian cycle, it can lead to dysregulation in the expression of circadian cycle regulatory genes, with potential health damage. In conclusion, IF may have the potential to be an adjuvant treatment to improve the reestablishment of hypothalamic responses in obesity.
RESUMEN
During overnight sleep, the longest postabsorptive and inactive phase of the day causes protein catabolism and loss. However, the daytime ingestion of dairy proteins has been shown to stimulate muscle protein synthesis and growth. This study compared the effects of pre-sleep supplementation of a protein blend (PB) composed of micellar casein (MCa) and whey protein (1:1) versus isolate MCa on the plasma levels of branched-chain amino acids (BCAAs) and the activation of the mechanistic target of rapamycin (mTOR) signaling, a critical intracellular pathway involved in the regulation of muscle protein synthesis. After 10 h of fasting during the active phase, rats were fed with a single dose of PB or MCa (5.6 g protein/kg of body mass) by gavage, and samples of blood and gastrocnemius muscle were collected at 30, 90, and 450 min. PB and MCa supplementations induced an increase (~3-fold, P < 0.001) of plasma BCAAs at 30 and 90 min. Most importantly, the stimulatory phosphorylation levels of mTOR and its downstream target p70 ribosomal protein S6 kinase (p70S6K) were similarly higher (~2.5-fold, P < 0.001) 30 and 90 min after MCa and PB. Plasma levels of leucine, isoleucine, valine, and overall BCAAs were correlated with the activation of mTOR (P < 0.001) and p70S6K (P < 0.001). MCa and PB supplementations before the inactive phase of rats resulted in an anabolic milieu in the skeletal muscle by inducing a transient increase in plasma BCAAs and a similar activation of the mTOR/p70S6K axis.
Asunto(s)
Músculo Esquelético , Animales , Caseínas , Suplementos Dietéticos , Leucina , Fosforilación , Ratas , Sirolimus , Serina-Treonina Quinasas TORRESUMEN
It has been suggested that eccentric contraction (EC) is associated with increases in serially arranged sarcomeres (sarcomerogenesis), while concentric contraction (CC) has been associated with serial sarcomeres decrease. Sarcomerogenesis following EC is thought to be a protective muscle adaptation, preventing muscle injury in future eccentric exercise bouts (repeated bout effect). However, the mechanisms underlying sarcomerogenesis in EC remain unknown, and the sarcomerogenic responses observed in response to EC and CC are contradictory. We measured sarcomere length, sarcomere length uniformity, serial sarcomere number, and fascicle length in gastrocnemius medialis, tibialis anterior, vastus medialis and vastus lateralis in sedentary (SED) mice, and in mice following protocols of moderate uphill (TRU) and downhill (TRD) training and uphill (OTU) and downhill (OTD) overtraining. We found pain sensitivity after the first bout of EC exercise on TRD and OTD followed by a normalized sensory response after four weeks of training, indicating a repeated bout effect. However, these findings were not associated with sarcomerogenesis, as serial sarcomere numbers did not increase in TRD and OTD skeletal muscle samples compared to controls (SED). However, we found a decrease in serial sarcomere number in VL and TA in OTU group mice, which was associated with a decrease in fascicle length and no change of sarcomere length at the tested joint configuration. We conclude that excessive concentric muscle contraction (OTU group mice), leads to a decrease in serial sarcomere number, while moderate or excessive eccentric training, did not result in sarcomerogenesis, as reported in the literature.