Transgenic mice expressing dominant-negative retinoic acid receptor (RAR) a specifically in the liver exhibit steatohepatitis, which leads to the development of liver tumors. Although the cause of steatohepatitis in these mice is unknown, diminished hepatic expression of insulin-like growth factor-1 suggests that insulin resistance may be involved. In the present study, we examined the effects of retinoids on insulin resistance in mice to gain further insight into the mechanisms responsible for this condition. Dietary administration of all-trans-retinoic acid (ATRA) significantly improved insulin sensitivity in C57BL/6J mice, which served as a model for high-fat, high-fructose diet-induced nonalcoholic fatty liver disease (NAFLD). The same effect was observed in genetically insulin-resistant KK-A y mice, occurring in concert with activation of leptin-signaling pathway proteins, including signal transducer and activator of transcription 3 (STAT3) and Janus kinase 2. However, such an effect was not observed in leptin-deficient ob/ob mice. ATRA treatment significantly up-regulated leptin receptor (LEPR) expression in the livers of NAFLD mice. In agreement with these observations, in vitro experiments showed that in the presence of leptin, ATRA directly induced LEPR gene expression through RARa, resulting in enhancement of STAT3 and insulin-induced insulin receptor substrate 1 phosphorylation. A selective RARa/b agonist, Am80, also enhanced hepatic LEPR expression and STAT3 phosphorylation and ameliorated insulin resistance in KK-A y mice. Conclusion: We discovered an unrecognized mechanism of retinoid action for the activation of hepatic leptin signaling, which resulted in enhanced insulin sensitivity in two mouse models of insulin resistance. Our data suggest that retinoids might have potential for treating NAFLD associated with insulin resistance. (HEPATOLOGY 2012;56:1319-1330

Purpose The present study investigated the effects of three consecutive days of endurance training under conditions of low energy availability (LEA) on the muscle glycogen content, muscle damage markers, endocrine regulation, and endurance capacity in male runners. Methods Seven male long-distance runners (19.9 ± 1.1 yr, 175.6 ± 4.7 cm, 61.4 ± 5.3 kg, maximal oxygen uptake [V˙O2max]: 67.5 ± 4.3 mL·kg−1·min−1) completed two trials consisting of three consecutive days of endurance training under LEA (18.9 ± 1.9 kcal·kg FFM−1·d−1) or normal energy availability (NEA) (52.9 ± 5.0 kcal·kg FFM−1·d−1). The order of the two trials was randomized, with a 2-wk interval between trials. The endurance training consisted of 75 min of treadmill running at 70% of V˙O2max. Muscle glycogen content, respiratory gas variables, and blood and urine variables were measured in the morning for three consecutive days of training (days 1–3) and on the following morning after training (day 4). As an indication of endurance capacity, time to exhaustion at 19.0 ± 0.8 km·h−1 to elicit 90% of V˙O2max was evaluated on day 4. Results During the training period, body weight, fat-free mass, and skeletal muscle volume were significantly reduced in LEA (P = 0.02 for body weight and skeletal muscle volume, P = 0.01 for fat-free mass). Additionally, muscle glycogen content was significantly reduced in LEA (~30%, P < 0.001), with significantly lower values than those in NEA (P < 0.001). Time to exhaustion was not significantly different between the two trials (~20 min, P = 0.39). Conclusions Three consecutive days of endurance training under LEA decreased muscle glycogen content with lowered body weight. However, endurance capacity was not significantly impaired.

BackgroundAcute exercise in the heat has been shown to reduce appetite. However, the influence of exercise in the cold on appetite regulation remains unclear. The aim of this study was to compare exercise-induced appetite regulation under three different environmental temperatures.MethodsEleven male participants completed three experimental trials on the following separate days: exercise in the heat (36°C), exercise at neutral temperature (24°C), and exercise in the cold (12°C). The exercise trials consisted of pedaling exercises for 30 min at 65% of maximal oxygen uptake (VO2max). Blood samples were collected repeatedly to determine plasma ghrelin, peptide YY (PYY) and other hormonal concentrations. Subjective feelings of hunger and tympanic temperature were also monitored.ResultsTympanic temperature was significantly higher in the 36°C trial than that of the other two trials (P < 0.05). The subjective feelings of hunger in the 36°C and 24°C trials were significantly lower than those in the 12°C trial (P < 0.05). Plasma ghrelin concentration decreased significantly with exercise in all conditions (P < 0.05), and the responses were not significantly different among the three conditions. Plasma PYY concentration increased significantly after the exercise in the 24°C trial only (P < 0.05), with no significant difference among the three trials.ConclusionsThese results suggest that exposure to hot or cold temperatures during exercise did not affect exercise-induced plasma ghrelin and PYY responses. However, the exercise-induced reduction of subjective hunger was significantly attenuated in a cold environment.

Sumi, D, Kojima, C, and Goto, K. Impact of endurance exercise in hypoxia on muscle damage, inflammatory and performance responses. J Strength Cond Res 32(4): 1053-1062, 2018-This study evaluated muscle damage and inflammatory and performance responses after high-intensity endurance exercise in moderate hypoxia among endurance athletes. Nine trained endurance athletes completed 2 different trials on different days: exercise under moderate hypoxia (H trial, FiO2 = 14.5%) and normoxia (N trial, FiO2 = 20.9%). They performed interval exercises (10 × 3-minute running at 95% of V[Combining Dot Above]O2max with 60-second of active rest at 60% of V[Combining Dot Above]O2max) followed by 30-minute of continuous running at 85% of V[Combining Dot Above]O2max under either hypoxic or normoxic conditions. Venous blood samples were collected 4 times: before exercise, 0, 60, and 120-minute after exercise. The time to exhaustion (TTE) during running at 90% of V[Combining Dot Above]O2max was also determined to evaluate endurance capacity 120-minute after the training session. The H trial induced a significantly greater exercise-induced elevation in the blood lactate concentration than did the N trial (p = 0.02), whereas the elevation in the exercise-induced myoglobin concentration (muscle damage marker) was significantly greater in the N trial than in the H trial (p = 0.005). There was no significant difference in plasma interleukin-6 (inflammatory marker) concentration between the H and N trials. The TTE was shorter in the N trial (613 ± 65 seconds) than in the H trial (783 ± 107 seconds, p = 0.02). In conclusion, among endurance athletes, endurance exercise under moderate hypoxic conditions did not facilitate an exercise-induced muscle damage response or cause a further reduction in the endurance capacity compared with equivalent exercise under normoxic conditions.