Time-restricted feeding combined with resistance exercise prevents obesity and improves lipid metabolism in the liver of mice fed a high-fat diet.

Nonalcoholic fatty liver disease (NAFLD), a condition characterized by the accumulation of fat in the liver, is estimated to be the most common liver disease worldwide. Obesity is a major risk factor and contributor, and, accordingly, weight loss can improve NAFLD. Previous studies in preclinical models of diet-induced obesity and fatty liver disease have shown the independent benefits of resistance exercise training (RT) and time-restricted feeding (TRF) in preventing weight gain and hepatic build-up of fat. Here, we tested the combined effect of TRF and RT on obesity and NAFLD in mice fed a high-fat diet. Our results showed that both TRF-8-h food access in the active phase-and RT-consisting of three weekly sessions of ladder climbing-attenuated body weight gain, improved glycemic homeostasis, and decreased the accumulation of lipids in the liver. TRF combined with RT improved the respiratory exchange rate, energy expenditure, and mitochondrial respiration in the liver. Furthermore, gene expression analysis in the liver revealed lower mRNA expression of lipogenesis and inflammation genes along with increased mRNA of fatty acid oxidation genes in the TRF + RT group. Importantly, combined TRF + RT was shown to be more efficient in preventing obesity and metabolic disorders. In conclusion, TRF and RT exert complementary actions compared with isolated interventions, with significant effects on metabolic disorders and NAFLD in mice.NEW & NOTEWORTHY Whether time-restricted feeding (TRF) combined with resistance exercise training (RT) may be more efficient compared with these interventions alone is still unclear. We show that when combined with RT, TRF provided additional benefits, being more effective in increasing energy expenditure, preventing weight gain, and regulating glycemic homeostasis than each intervention alone. Thus, our results demonstrate that TRF and RT have complementary actions on some synergistic pathways that prevented obesity and hepatic liver accumulation.

Omega-3 pleiad: The multipoint anti-inflammatory strategy.

Omega 3 (ω3) fatty acids have been described since the 1980s as promising anti-inflammatory substances. Prostaglandin and leukotriene modulation were exhaustively explored as the main reason for ω3 beneficial outcomes. However, during the early 2000s, after the human genome decoding advent, the nutrigenomic approaches exhibited an impressive plethora of ω3 targets, now under the molecular point of view. Different G protein-coupled receptors (GPCRs) recognizing ω3 and its derivatives appear to be responsible for blocking inflammation and insulin-sensitizing effects. A new class of ω3-derived substances, such as maresins, resolvins, and protectins, increases ω3 actions. Inflammasome disruption, the presence of GPR120 on immune cell surfaces, and intracellular crosstalk signaling mediated by PPARγ compose the last discoveries regarding the multipoint anti-inflammatory targets for this nutrient. This review shows a detailed mechanistic proposal to understand ω3 fatty acid action over the inflammatory environment in the background of several chronic diseases.

Effects of short-term physical training on the interleukin-15 signalling pathway and glucose tolerance in aged rats.

PURPOSE: Interleukin-15 (IL-15) is a myokine that has been proposed to modulate skeletal muscle and adipose tissue mass, as well as insulin sensitivity. However, the evidence suggesting a role for IL-15 in improving whole-body insulin sensitivity and decreasing adiposity comes mainly from studies using supraphysiological levels of this cytokine. This study examined the effect of a short-term exercise training protocol on the protein content of IL-15, it's signaling pathway, and glucose tolerance in aged rats. METHODS: Fourteen Wistar rats were divided into Young Sedentary (Young, n = 4); Old Sedentary (Old, n = 5); Old Exercise (Old.Exe, n = 5) groups. The animals from the exercised group were submitted to a short-term physical exercise protocol for five days. At the end of physical training and after 16 h of the last exercise session, the animals were euthanized, and tissue collection was done. RESULTS: Physical exercise decreased epididymal and mesenteric fat mass and promoted positive effects on glucose tolerance and insulin sensitivity. Muscle IL-15 protein levels were not changed following the short-term physical exercise training with no alterations in the post-exercise IL-15-JAK/STAT signaling pathway. We found a tendency to increased HIF1α and a significant increase in its regulator, PHD2, in the skeletal muscle after exercise. CONCLUSION: The elderly rats submitted to short-term aerobic physical training did not present skeletal muscle alteration in the protein content of the IL-15 and IL-15-JAK/STAT signaling pathway. However, short-term aerobic physical training was able to modulate the expression of HIF1α and its regulator PHD2, suggesting an essential role of these proteins in improving post-exercise glucose tolerance and insulin sensitivity in elderly rats.

Short-Term Combined Exercise Improves Inflammatory Profile in the Retina of Obese Mice.

Excess of adipose tissue increases the concentration of proinflammatory cytokines, triggering a subclinical inflammatory condition. This inflammatory profile contributes to retina damage, which can lead to retinal dysfunction and reduced vision. Regularly practicing both aerobic and strength exercises is well known for promoting anti-inflammatory effects on different organs in the peripheral and central regions. However, the effects of combined physical exercise (CPE; strength + aerobic) on the inflammatory process in the retina tissue are not yet known. This study aimed to investigate the effects of CPE on the inflammatory profile of the retina in obese mice. Swiss mice were distributed into control, sedentary obese, and trained obese groups. The trained obese group was subjected to short-term CPE, 1 h/day, for 7 days. The CPE was composed of aerobic and strength exercises in the same exercise session. The strength exercise protocol consisted of 10 climbing series, with 12 ± 1 dynamic climbing movements at 70% of the maximum voluntary carrying capacity (MVCC), and the aerobic exercise protocol consisted of 30 min of treadmill running, with an intensity of 75% of the exhaust velocity. Subsequently, the retina was excised and analyzed by Western blot. Obese animals presented impairment on glucose homeostasis and elevated levels of proinflammatory proteins in the serum and retina; however, CPE was effective in reversing these parameters, independently of changes in body adiposity. Therefore, for the first time, we have shown that short-term CPE can be an important strategy to treat an inflammatory profile in the retina.

Rock protein as cardiac hypertrophy modulator in obesity and physical exercise.

Obesity and cardiovascular diseases are worldwide public health issues. In this review, we discussed the participation of ROCK protein in cardiac hypertrophy, mainly through the modulation of leptin and insulin signaling pathways. Leptin plays a role in cardiovascular disease development and, through the Rho-associated protein kinase (ROCK), promotes cardiac hypertrophy. ROCK protein, is regulated by small Rho-GTPases and has two isoforms with high homology. ROCK is able to activate the MAP kinase (MAPK) pathway and modulate insulin signaling in the heart, participating in cardiac hypertrophy development of concentric and eccentric left ventricle growth. Although different types of stimulus can lead to morphologically antagonistic heart growth, physical exercise promotes improvements in hemodynamic function, emerging as a promising non-pharmacological tool to improve overall health. Leptin can activate ROCK in a pathological way, increasing MAPK activity and decreasing insulin signaling via insulin receptor substrate 1 (IRS1) serine 307 residue phosphorylation, phosphatase and tensin homolog, and protein kinase Cß2. In turn, physical exercise decreases leptin levels and positively modulates insulin signaling as well as increases ROCK-dependent IRS1 (Ser632/635) phosphorylation, improving phosphatidylinositol 3-kinase/protein kinase B axis and promoting physiologic heart growth. Currently, there is a lack of studies about differences in ROCK isoforms, especially during exercise and/or obesity. However, the understanding of its biological function and the complex mechanism underlying the distinct types of cardiac hypertrophy development can be a useful tool in the improvement and treatment of cardiovascular outcomes.

Apolipoprotein J is a hepatokine regulating muscle glucose metabolism and insulin sensitivity.

Crosstalk between liver and skeletal muscle is vital for glucose homeostasis. Hepatokines, liver-derived proteins that play an important role in regulating muscle metabolism, are important to this communication. Here we identify apolipoprotein J (ApoJ) as a novel hepatokine targeting muscle glucose metabolism and insulin sensitivity through a low-density lipoprotein receptor-related protein-2 (LRP2)-dependent mechanism, coupled with the insulin receptor (IR) signaling cascade. In muscle, LRP2 is necessary for insulin-dependent IR internalization, an initial trigger for insulin signaling, that is crucial in regulating downstream signaling and glucose uptake. Of physiologic significance, deletion of hepatic ApoJ or muscle LRP2 causes insulin resistance and glucose intolerance. In patients with polycystic ovary syndrome and insulin resistance, pioglitazone-induced improvement of insulin action is associated with an increase in muscle ApoJ and LRP2 expression. Thus, the ApoJ-LRP2 axis is a novel endocrine circuit that is central to the maintenance of normal glucose homeostasis and insulin sensitivity.