Associating Inulin with a Pea Protein Improves Fast-Twitch Skeletal Muscle Mass and Muscle Mitochondrial Activities in Old Rats.

Aging is associated with a decline in muscle mass and function, leading to increased risk for mobility limitations and frailty. Dietary interventions incorporating specific nutrients, such as pea proteins or inulin, have shown promise in attenuating age-related muscle loss. This study aimed to investigate the effect of pea proteins given with inulin on skeletal muscle in old rats. Old male rats (20 months old) were randomly assigned to one of two diet groups for 16 weeks: a 'PEA' group receiving a pea-protein-based diet, or a 'PEA + INU' group receiving the same pea protein-based diet supplemented with inulin. Both groups showed significant postprandial stimulation of muscle p70 S6 kinase phosphorylation rate after consumption of pea proteins. However, the PEA + INU rats showed significant preservation of muscle mass with time together with decreased MuRF1 transcript levels. In addition, inulin specifically increased PGC1-α expression and key mitochondrial enzyme activities in the plantaris muscle of the old rats. These findings suggest that dietary supplementation with pea proteins in combination with inulin has the potential to attenuate age-related muscle loss. Further research is warranted to explore the underlying mechanisms and determine the optimal dosage and duration of intervention for potential translation to human studies.

Induction of ATF4-Regulated Atrogenes Is Uncoupled from Muscle Atrophy during Disuse in Halofuginone-Treated Mice and in Hibernating Brown Bears.

Activating transcription factor 4 (ATF4) is involved in muscle atrophy through the overexpression of some atrogenes. However, it also controls the transcription of genes involved in muscle homeostasis maintenance. Here, we explored the effect of ATF4 activation by the pharmacological molecule halofuginone during hindlimb suspension (HS)-induced muscle atrophy. Firstly, we reported that periodic activation of ATF4-regulated atrogenes (Gadd45a, Cdkn1a, and Eif4ebp1) by halofuginone was not associated with muscle atrophy in healthy mice. Secondly, halofuginone-treated mice even showed reduced atrophy during HS, although the induction of the ATF4 pathway was identical to that in untreated HS mice. We further showed that halofuginone inhibited transforming growth factor-ß (TGF-ß) signalling, while promoting bone morphogenetic protein (BMP) signalling in healthy mice and slightly preserved protein synthesis during HS. Finally, ATF4-regulated atrogenes were also induced in the atrophy-resistant muscles of hibernating brown bears, in which we previously also reported concurrent TGF-ß inhibition and BMP activation. Overall, we show that ATF4-induced atrogenes can be uncoupled from muscle atrophy. In addition, our data also indicate that halofuginone can control the TGF-ß/BMP balance towards muscle mass maintenance. Whether halofuginone-induced BMP signalling can counteract the effect of ATF4-induced atrogenes needs to be further investigated and may open a new avenue to fight muscle atrophy. Finally, our study opens the way for further studies to identify well-tolerated chemical compounds in humans that are able to fine-tune the TGF-ß/BMP balance and could be used to preserve muscle mass during catabolic situations.

Impact of Eccentric or Concentric Training on Body Composition and Energy Expenditure.

PURPOSE: To compare the effects of 8-wk eccentric (ECC) versus concentric (CON) training using downhill and uphill running in rats on whole body composition, bone mineral density (BMD), and energy expenditure. METHODS: Animals were randomly assigned to one of the following groups: 1) control (CTRL), 2) +15% uphill-running slope (CON), 3) -15% downhill-running slope (ECC15), and 4) -30% downhill-running slope (ECC30). Those programs enabled to achieve conditions of isopower output for CON and ECC15 and of iso-oxygen uptake (V˙O2) for CON and ECC30. Trained rats ran 45 min at 15 m·min five times per week. Total body mass, fat body mass, and lean body mass (LBM) measured through EchoMRI™, and 24-h energy expenditure including basal metabolic rate (BMR) assessed using PhenoMaster/LabMaster™ cage system were obtained before and after training. At sacrifice, the right femur was collected for bone parameters analysis. RESULTS: Although total body mass increased in all groups over the 8-wk period, almost no change occurred for fat body mass in exercised groups (CON, -4.8 ± 6.18 g; ECC15, 0.6 ± 3.32 g; ECC30, 2.6 ± 6.01 g). The gain in LBM was mainly seen for ECC15 (88.9 ± 6.85 g) and ECC30 (101.6 ± 11.07 g). ECC was also seen to positively affect BMD. An increase in BMR from baseline was seen in exercise groups (CON, 13.9 ± 4.13 kJ·d; ECC15, 11.6 ± 5.10 kJ·d; ECC30, 18.3 ± 4.33 kJ·d) but not in CTRL one. This difference disappeared when BMR was normalized for LBM. CONCLUSIONS: Results indicate that for iso-V˙O2 training, the impact on LBM and BMD is enhanced with ECC as compared with CON, and that for isopower but lower V˙O2 ECC, an important stimulus for adaptation is still observed. This provides further insights for the use of ECC in populations with cardiorespiratory exercise limitations.