Cast immobilization of hindlimb upregulates sarcolipin expression in atrophied skeletal muscles and increases thermogenesis in C57BL/6J mice.

Mechanical unloading impairs cytosolic calcium (Ca2+) homeostasis in skeletal muscles. In this study, we investigated whether sarco(endo)plasmic reticulum Ca2+-ATPase (SERCA) itself or one of the regulators of the Ca2+ SERCA pump, sarcolipin (SLN), is altered to deregulate Ca2+ homeostasis in cast immobilized, atrophied muscles. Hindlimb muscles of 8-wk-old male C57BL/6J mice were subjected to bilateral cast immobilization for 2 wk. Two-week-cast immobilization induced both body weight and skeletal muscle loss. Highly phosphorylated Ca2+/calmodulin-dependent protein kinase II in the atrophied muscles suggested that cytosolic Ca2+ concentration was elevated. Extremely high expression levels of SLN mRNA and protein were observed in the atrophied muscles. Upregulation of SLN at the transcriptional level was supported by low RCAN1 expression, which is a negative regulator of SLN. We treated C2C12 cells with dexamethasone to mimic muscle atrophy in vitro and showed a direct relationship between high SLN mRNA expression and low Ca2+ uptake by sarcoplasmic reticulum. Since SLN reportedly plays a role in nonshivering thermogenesis, we performed a cold tolerance test of the whole body. As a result, we found that mice with cast immobilization showed high cold tolerance, suggesting that cast immobilization promoted whole body thermogenesis. Although the activity level was decreased during cast immobilization without change in food intake, adipose tissue weights also decreased significantly after cast immobilization. Concomitantly, we conclude that cast immobilization of hindlimb increased thermogenesis in C57Bl/6J mice, probably via high expression of SLN.

Moderate Intensity Cycling Exercise after Upper Extremity Resistance Training Interferes Response to Muscle Hypertrophy but Not Strength Gains.

The purpose of the present study was to examine the effect of 30-min moderate intensity cycling exercise immediately after upper-body resistance training on the muscle hypertrophy and strength gain. Fourteen subjects were randomly divided between two groups. One group performed moderate intensity (55% of maximum oxygen consumption [VO2max], 30 min) cycle training immediately after arm resistance training as concurrent training (CT; n = 7, age: 21.8 ± 0.7 years, height: 1.68 ± 0.06 m, weight: 60.3 ± 7.4 kg); the second group performed the same endurance and arm RT on separate days as control group (SEP; n=7, age: 22.1 ± 0.7 years, height: 1.76 ± 0.05 m, weight: 63.8 ± 3.6 kg). The supervised progressive RT program was designed to induce muscular hypertrophy (3-5 sets of 10 repetitions) with bilateral arm-curl exercise using 75% of the one repetition maximum (1RM) with 2-min rest intervals. The RT program was performed for 8 weeks, twice per week. Muscle cross-sectional area (CSA), 1RM, and VO2max were measured pre- and post-training. Significant increases in muscle CSA from pre- to post-training were observed in both the SEP (p = 0.001, effect size [ES] = 0.84) and the CT groups (p = 0.004, ES = 0.45). A significant increase in 1RM from pre- to post-training was observed in the SEP (p = 0.025, ES = 0.91) and CT groups (p = 0.001, ES = 2.38). There were no interaction effects (time × group) for CSA, 1RM, or VO2max. A significantly higher percentage change of CSA was observed in the SEP group (12.1 ± 4.9%) compared to the CT group (5.0 ± 2.7%, p = 0.029), but no significant difference was observed in the 1RM (SEP: 19.8 ± 16.8%, CT: 24.3 ± 11.1%). The data suggest that significant improvement of CSA and strength can be expected with progressive resistance training with subsequent endurance exercise performed immediately or on a different day. Changes in CSA might be affected by subsequent cycling exercise after 8 weeks of training.

Apple polyphenols induce browning of white adipose tissue.

We and others have shown that apple polyphenols decrease adipose tissue mass. To better understand the underlying mechanisms and to expand clinical applicability, we herein examine whether apple polyphenols induce adipose thermogenic adaptations (browning) and prevent diet-induced obesity and related insulin resistance. In mice fed a standard diet, daily apple polyphenol consumption induced thermogenic adaptations in inguinal white adipose tissue (iWAT), based on increases in the expression of brown/beige adipocyte selective genes (Ucp1, Cidea, Tbx1, Cd137) and protein content of uncoupling protein 1 and mitochondrial oxidative phosphorylation enzymes. Among the upstream regulatory factors of browning, fibroblast growth factor 21 (FGF21) and peroxisome proliferator-activated receptor gamma coactivator 1 α (PGC-1α) levels were concomitantly up-regulated by apple polyphenols. In the primary cell culture experiment, the results did not support a direct action of apple polyphenols on beige adipogenesis. Instead, apple polyphenols increased tyrosine hydroxylase (a rate-limiting enzyme of catecholamine synthesis) in iWAT, which activates the adipocyte thermogenic program possibly via intratissue cellular communications. In high-fat fed mice, apple polyphenols induced beige adipocyte development in iWAT, reduced fat accumulation, and increased glucose disposal rates in the glucose and insulin tolerance tests. Taken together, dietary administration of apple polyphenols induced beige adipocyte development in iWAT possibly via activation/induction of the peripheral catecholamine synthesis-FGF21-PGC-1α cascade. Results from diet-induced obese mice indicate that apple polyphenols have therapeutic potential for obesity and related metabolic disorders.