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Senescence impairs liver physiology, mitochondrial function and circadian regulation, resulting in systemic metabolic dysregulation. Given the limited research on the effects of combined exercise on an ageing liver, this study aimed to evaluate its impact on liver metabolism, circadian rhythms and mitochondrial function in senescence‐accelerated mouse‐prone 8 (SAMP8) and senescence‐accelerated mouse‐resistant 1 (SAMR1) mice. Histological, reverse transcription quantitative polymerase chain reaction (RT‐qPCR) and immunoblotting analyses were conducted, supplemented by transcriptomic data sets and AML12 hepatocyte studies. Sedentary SAMP8 mice exhibited decreased muscle strength, reduced mitochondrial complex I levels and increased lipid droplet accumulation. In contrast, combined exercise mitigated muscle strength loss, upregulated proteins involved in mitochondrial complexes (CIII, CIV, CV) and increased Bmal1 messenger RNA (mRNA) expression in the liver. These molecular adaptations are associated with healthier liver phenotypes and may influence metabolic function and cellular longevity. Notably, elevated lipid content in aged mice was reduced post‐exercise, indicating liver benefits even after a relatively short intervention. The combined exercise regimen did not improve aerobic capacity, likely due to the low volume and brief duration of running. Moreover, no significant effects were observed in SAMR1 mice, possibly because the training intensity was insufficient for younger, healthier animals. These findings underscore the potential of combined strength and endurance exercise to attenuate age‐related liver dysfunction, particularly in ageing populations. [ABSTRACT FROM AUTHOR]

Introduction: Obesity presents with structural and functional hypothalamic dysfunction. However, it is unclear whether weight loss can lead to hypothalamic changes. We therefore aimed to conduct a systematic review and meta-analysis to determine the effect of body mass reduction in obese individuals on hypothalamic structure and function. Methods: PubMed, Embase and Cochrane databases were searched for studies that reported the change in hypothalamic structure and function after weight loss. Qualitative and quantitative analyses were performed on magnetic resonance imaging techniques, medio-basal hypothalamus T2-relaxation time, blood oxygen level dependent (BOLD) contrast, voxel-based morphometry (VBM) and biomarkers including glucose, insulin, leptin, ghrelin and inflammatory markers of interleukins. Mean differences between pre- and post-weight loss and 95% confidence intervals (CIs) were pooled using random-effects models. Results: Thirteen pre–post studies were included, of which six accounted for the meta-analysis. Studies showed a favorable decrease in T2-relaxation time (n = 1), favorable change in hypothalamic activity after weight loss on BOLD contrast (n = 4), with higher peak activities after surgical weight loss (n = 2). No differences were found in the gray matter density of the hypothalamus on VBM (n = 1). Pooled mean differences between pre- and post-surgical weight loss revealed a decrease of 8.53 mg/dl (95% CI: 5.17, 11.9) in glucose, 7.73 pmol/l (95% CI: 5.07, 10.4) in insulin, 15.5 ng/ml (95% CI: 9.40, 21.6) in leptin, 142.9 pg/ml (95% CI: 79.0, 206.8) in ghrelin and 9.43 pg/ml (95% CI: −6.89, 25.7) in IL-6 level. Conclusions: Our study showed weight reduction in obesity led to limited structural change and significant functional changes in the hypothalamus. [ABSTRACT FROM AUTHOR]

Many conditions, such as inflammation and physical exercise, can induce endoplasmic reticulum (ER) stress. Toll‐like Receptor 4 (TLR4) can trigger inflammation and ER stress events. However, there are still no data in the literature regarding the role of TLR4 in ER stress during exercise in skeletal muscle. Therefore, the current investigation aimed to verify the responses of ER stress markers in wild‐type (WT) and Tlr4 global knockout (KO) mice after acute and chronic physical exercise protocols. Eight‐week‐old male WT and KO mice were submitted to acute (moderate or high intensity) and chronic (4‐week protocol) treadmill exercises. Under basal conditions, KO mice showed lower performance in the rotarod test. Acute high‐intensity exercise increased eIF2α protein in the WT group. After the acute high‐intensity exercise, there was an increase in Casp3 and Ddit3 mRNA for the KO mice. Acute moderate exercise increased the cleaved Caspase‐3/Caspase‐3 in the KO group. In response to chronic exercise, the KO group showed no improvement in any performance evaluation. The 4‐week chronic protocol did not generate changes in ATF6, CHOP, p‐IRE1α, p‐eIF2α/eIF2α, and cleaved Caspase‐3/Caspase‐3 ratio but reduced BiP protein compared with the KO‐Sedentary group. These results demonstrate the global deletion of Tlr4 seems to have the same effects on UPR markers of WT animals after acute and chronic exercise protocols but decreased performance. The cleaved Caspase‐3/Caspase‐3 ratio may be activated by another pathway other than ER stress in Tlr4 KO animals. Key points: While acute high‐intensity exercise increased the Casp3 and Ddit3 mRNA in KO mice, acute moderate‐intensity exercise increased the cleaved Caspase‐3/Caspase‐3 in the same group.Under basal conditions, Tlr4 KO mice showed lower performance in the rotarod test. In response to chronic exercise, the Tlr4 KO group showed no improvement in any performance evaluation.The global deletion of Tlr4 seems to have the same effects on UPR markers of WT animals after acute and chronic exercise protocols but decreased performance and seems to activate the apoptosis pathway. Significance statement The endoplasmic reticulum (ER) is responsible for translating and folding most proteins in our body. Protein homeostasis imbalance leads to malformed proteins in the ER lumen, and their accumulation leads to ER stress. Toll‐like Receptor 4 (TLR4) can trigger inflammation, and TLR4 global knockout (KO) mice are protected against ER stress. Furthermore, physical exercise can reduce the TLR4 in the cell. As inflammation seems to affect physical exercise‐related ER stress, the present study investigated the relationship between TLR4 and ER stress after physical exercise in skeletal muscle. [ABSTRACT FROM AUTHOR]

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Abstract Background The influence of feed restriction and different diet's caloric value on the aerobic and anaerobic capacity is unclear in the literature. Thus, the objectives of this study were to determine the possible influences of two diets with different caloric values and the influence of feed restriction on the aerobic (anaerobic threshold: AT) and anaerobic (time to exhaustion: Tlim) variables measured by a lactate minimum test (LM) in rats. Methods We used 40 adult Wistar rats. The animals were divided into four groups: ad libitum commercial Purina® diet (3028.0 Kcal/kg) (ALP), restricted commercial Purina® diet (RAP), ad libitum semi-purified AIN-93 diet (3802.7 Kcal/kg) (ALD) and restricted semi-purified AIN-93 diet (RAD). The animals performed LM at the end of the experiment, 48 h before euthanasia. Comparisons between groups were performed by analysis of variance (p < 0,05). Results At the end of the experiment, the weights of the rats in the groups with the restricted diets were significantly lower than those in the groups with ad libitum diet intakes. In addition, the ALD group had higher amounts of adipose tissue. With respect to energetic substrates, the groups subjected to diet restriction had significantly higher levels of liver and muscle glycogen. There were no differences between the groups with respect to AT; however, the ALD group had lower lactatemia at the AT intensity and higher Tlim than the other groups. Conclusions We conclude that dietary restriction induces changes in energetic substrates and that ad libitum intake of a semi-purified AIN-93 diet results in an increase in adipose tissue, likely reducing the density of the animals in water and favouring their performance during the swimming exercises.

To evaluate the effects of taurine supplementation associated or not with chronic exercise on body composition, mitochondrial function, and expression of genes related to mitochondrial activity and lipid oxidation in the subcutaneous white adipose tissue (scWAT) of obese women. A randomized and double-blind trial was developed with 24 obese women (BMI 33.1 ± 2.9 kg/m2, 32.9 ± 6.3 y) randomized into three groups: Taurine supplementation group (Tau, n = 8); Exercise group (Ex, n = 8); Taurine supplementation + exercise group (TauEx, n = 8). The intervention was composed of 3 g of taurine or placebo supplementation and exercise training for eight weeks. Anthropometry, body fat composition, indirect calorimetry, scWAT biopsy for mitochondrial respiration, and gene expression related to mitochondrial activity and lipid oxidation were assessed before and after the intervention. No changes were observed for the anthropometric characteristics. The Ex group presented an increased resting energy expenditure rate, and the TauEx and Ex groups presented increased lipid oxidation and a decreased respiratory quotient. Both trained groups (TauEx and Ex) demonstrated improved scWAT mitochondrial respiratory capacity. Regarding mitochondrial markers, no changes were observed for the Tau group. The TauEx group had higher expression of CIDEA, PGC1a, PRDM16, UCP1, and UCP2. The genes related to fat oxidation (ACO2 and ACOX1) were increased in the Tau and Ex groups, while only the TauEx group presented increased expression of CPT1 , PPARa, PPARγ, LPL, ACO1, ACO2, HSL, ACOX1, and CD36 genes. Taurine supplementation associated with exercise improved lipid metabolism through the modulation of genes related to mitochondrial activity and fatty acid oxidation, suggesting a browning effect in the scWAT of obese women. Taurine supplementation only increased the expression of fat oxidation genes (ACO2 and ACOX1). Exercise increased energy metabolism and the expression of fat oxidation genes in the subcutaneous white adipose tissue. The association between taurine supplementation and exercise promoted additional effects to exercise by increasing energy expenditure, and upregulating mitochondrial respiratory capacity and the expression of genes related to mitochondrial metabolism and fat oxidation in the subcutaneous adipose tissue (scWAT) of obese women. [Display omitted] [ABSTRACT FROM AUTHOR]

The hypothalamus plays a critical role in the control of food consumption and energy expenditure. Fatty diets can elicit an inflammatory response in specific hypothalamic cells, including astrocytes, tanycytes, and microglia, disrupting anorexigenic signals in region-specific hypothalamic neurons, contributing to overeating and body weight gain. In this study, we present an update regarding the knowledge of the effects of physical exercise on inflammatory signaling and circuits to control hunger in the hypothalamus in obesity conditions. To try to understand changes in the hypothalamus, we review the use of magnetic resonance/anorexigenic hormone analysis in humans, as well as in animal models to explore the physiological and molecular mechanism by which exercise modulates satiety signals, such as the central antiinflammatory response, myokine delivery from skeletal muscle, and others. The accumulation of scientific evidence in recent years allows us to understand that exercise contributes to weight control, and it is managed by mechanisms that go far beyond "burning calories.". [ABSTRACT FROM AUTHOR]

Autophagy plays an essential role in body homeostasis achievement. One of the main proteins involved in this process is the LC3I, which, after lipidation, leads to the formation of LC3II that participates in the formation and maturation of autophagosome. This descriptive study verified the responses of LC3II to LC3I proteins, as well as the time-course of this ratio in mice livers after different types of acute physical exercise protocols. Eight-week-old male C57BL/6 mice were maintained three per cage with controlled temperature (22±2 °C) on a 12:12-h light-dark normal cycle with food (Purina chow) and water ad libitum. Mice were randomly divided into four groups: control (CT, sedentary mice), resistance (RE, submitted to a single bout of resistance exercise), endurance (EE, submitted to a single bout of endurance exercise), and concurrent (CE, submitted to a single bout of endurance combined with resistance exercise). The mice livers were extracted and used for the immunoblotting technique. The hepatic LC3B II/I ratio for the RE and EE groups were not altered during the different time-points. For the CE group, there was a decrease in this ratio 12h after exercise compared to time 0 and 18h. Also, the hepatic LC3B II/I ratios were not different among the acute physical exercise protocols along the time-course. The hepatic LC3B II/I ratio was not influenced by the endurance and resistance protocols but decreased in response to the concurrent protocol at 12h after the stimulus. [ABSTRACT FROM AUTHOR]