[Abstract unavailable

Key points• Contradictory findings have been reported concerning the function of irisin and its precursor gene, skeletal muscle FNDC5, in energy homeostasis and metabolic health, and the associated regulatory role of exercise and PGC-1α.• We analysed the effects of different short-and long-term exercise regimens on muscle FNDC5and PGC-1α, and serum irisin, and studied the associations of irisin and FNDC5 with health parameters.• FNDC5 and serum irisin did not change after acute aerobic, long-term endurance training or endurance training combined with resistance exercise (RE) training, or associate with metabolic disturbances. A single RE bout increased FNDC5 mRNA in young, but not older men (27 vs. 62 years). Changes in PGC-1α or serum irisin were not consistently accompanied by changes in FNDC5.• Our data suggest that the effects of exercise on FNDC5 and irisin are not consistent, and that their role in health is questionable. Moreover, the regulatory mechanisms should be studied further.Abstract Recently, contradictory findings have been reported concerning the function of irisin and its precursor gene, skeletal muscle FNDC5, in energy homeostasis, and the associated regulatory role of exercise and PGC-1α. We therefore evaluated whether muscle FNDC5 mRNA and serum irisin are exercise responsive and whether PGC-1α expression is associated with FNDC5 expression. The male subjects in the study performed single exercises: (1) 1 h low-intensity aerobic exercise (AE) (middle-aged, n = 17), (2) a heavy-intensity resistance exercise (RE) bout (young n = 10, older n = 11) (27 vs. 62 years), (3) long-term 21 weeks endurance exercise (EE) training alone (twice a week, middle-aged, n = 9), or (4) combined EE and RE training (both twice a week, middle-aged, n = 9). Skeletal muscle mRNA expression was analysed by quantitative PCR and serum irisin by ELISA. No significant changes were observed in skeletal muscle PGC-1α, FNDC5 and serum irisin after AE, EE training or combined EE + RE training. However, a single RE bout increased PGC-1α by 4-fold in young and by 2-fold in older men, while FNDC5 mRNA only increased in young men post-RE, by 1.

Worries about the potential negative consequences of popular fat loss regimens for aesthetic purposes in normal weight females have been surfacing in the media. However, longitudinal studies investigating these kinds of diets are lacking. The purpose of the present study was to investigate the effects of a 4-month fat-loss diet in normal weight females competing in fitness-sport. In total 50 participants finished the study with 27 females (27.2 ± 4.1 years) dieting for a competition and 23 (27.7 ± 3.7 years) acting as weight-stable controls. The energy deficit of the diet group was achieved by reducing carbohydrate intake and increasing aerobic exercise while maintaining a high level of protein intake and resistance training in addition to moderate fat intake. The diet led to a ~12% decrease in body weight (P < 0.001) and a ~35–50% decrease in fat mass (DXA, bioimpedance, skinfolds, P < 0.001) whereas the control group maintained their body and fat mass (diet × group interaction P < 0.001). A small decrease in lean mass (bioimpedance and skinfolds) and in vastus lateralis muscle cross-sectional area (ultrasound) were observed in diet (P < 0.05), whereas other results were unaltered (DXA: lean mass, ultrasound: triceps brachii thickness). The hormonal system was altered during the diet with decreased serum concentrations of leptin, triiodothyronine (T3), testosterone (P < 0.001), and estradiol (P < 0.01) coinciding with an increased incidence of menstrual irregularities (P < 0.05). Body weight and all hormones except T3 and testosterone returned to baseline during a 3–4 month recovery period including increased energy intake and decreased levels aerobic exercise. This study shows for the first time that most of the hormonal changes after a 35–50% decrease in body fat in previously normal-weight females can recover within 3–4 months of increased energy intake.

BackgroundCancer cachexia increases morbidity and mortality, and blocking of activin receptor ligands has improved survival in experimental cancer. However, the underlying mechanisms have not yet been fully uncovered.MethodsThe effects of blocking activin receptor type 2 (ACVR2) ligands on both muscle and non‐muscle tissues were investigated in a preclinical model of cancer cachexia using a recombinant soluble ACVR2B (sACVR2B‐Fc). Treatment with sACVR2B‐Fc was applied either only before the tumour formation or with continued treatment both before and after tumour formation. The potential roles of muscle and non‐muscle tissues in cancer cachexia were investigated in order to understand the possible mechanisms of improved survival mediated by ACVR2 ligand blocking.ResultsBlocking of ACVR2 ligands improved survival in tumour‐bearing mice only when the mice were treated both before and after the tumour formation. This occurred without effects on tumour growth, production of pro‐inflammatory cytokines or the level of physical activity. ACVR2 ligand blocking was associated with increased muscle (limb and diaphragm) mass and attenuation of both hepatic protein synthesis and splenomegaly. Especially, the effects on the liver and the spleen were observed independent of the treatment protocol. The prevention of splenomegaly by sACVR2B‐Fc was not explained by decreased markers of myeloid‐derived suppressor cells. Decreased tibialis anterior, diaphragm, and heart protein synthesis were observed in cachectic mice. This was associated with decreased mechanistic target of rapamycin (mTOR) colocalization with late‐endosomes/lysosomes, which correlated with cachexia and reduced muscle protein synthesis.ConclusionsThe prolonged survival with continued ACVR2 ligand blocking could potentially be attributed in part to the maintenance of limb and respiratory muscle mass, but many observed non‐muscle effects suggest that the effect may be more complex than previously thought. Our novel finding showing decreased mTOR localization in skeletal muscle with lysosomes/late‐endosomes in cancer opens up new research questions and possible treatment options for cachexia.