A novel nutritional supplement prevents muscle loss and accelerates muscle mass recovery in caloric-restricted mice

Abstract

a b s t r a c tBackground: Muscle atrophy is defined as decreased muscle mass, associated with aging as well as with various chronic diseases and is a fundamental cause of frailty, functional decline and disability. Frailty represents a huge potential public health issue worldwide with high impact on healthcare costs. A major clinical issue is therefore to devise new strategies preventing muscle atrophy. In this study, we tested the efficacy of Vital01, a novel oral nutritional supplement (ONS), on body weight and muscle mass using a caloric restriction-induced mouse model for muscle atrophy. Methods: Mice were calorically restricted for 2 weeks to induce muscle atrophy: one control group received 60% kcal of the normal chow diet and one intervention group received 30% kcal chow and 30 kcal% Vital01. The effects on body weight, lean body mass, muscle histology and transcriptome were assessed. In addition, the effects of Vital01, in mice with established muscle atrophy, were assessed and compared to a standard ONS. To this end, mice were first calorically restricted on a 60% kcal chow diet and then refed with either 100 kcal% chow, a mix of Vital01 (receiving 60% kcal chow and 40 kcal% Vital01) or with a mix of standard, widely prescribed ONS (receiving 60 kcal% chow and 40 kcal% Fortisip Compact). Results: Vital01 attenuated weight loss (−15% weight loss for Vital01 vs. −25% for control group, p b 0.01) and loss of muscle mass (Vital01 with −13%, −12% and −18%, respectively, for gastrocnemius, quadriceps and tibialis vs. 25%, −23% and −28%, respectively, for control group, all p b 0.05) and also restored body weight, fat and muscle mass more efficiently when compared to Fortisip Compact. As assessed by transcriptome analysis and Western blotting of key proteins (e.g. phospoAKT, mTOR and S6K), Vital01 attenuated the catabolic and anabolic signaling pathways induced by caloric restriction and modulated inflammatory and mitochondrial pathways. In addition, Vital01 affected pathways related to matrix proteins/collagens homeostasis and tended to reduce caloric restriction-induced collagen fiber density in the quadriceps (with −27%, p = 0.051). Conclusions:We demonstrate that Vital01 preserves muscle mass in a calorically restricted mouse model for muscle atrophy. Vital01 had preventive effects when administered during development of muscle atrophy. Furthermore, when administered in a therapeutic setting to mice with established muscle atrophy, Vital01 rapidly restored body weight and accelerated the recurrence of fat and lean body mass more efficiently than Fortisip Compact. Bioinformatics analysis of gene expression data identified regulatory pathways that were specifically influenced by Vital01 in muscle.

The Yucatan minipig model: A new preclinical model of malnutrition induced by a low-calorie/low-protein diet

“…The trends for downregulation of muscle mRNA myostatin levels we report in muscle of malnourished minipigs may play a role in Akt activation since this transforming growth factor is recognized to negatively regulate the activity of Akt [64]. Even if previous studies observed a similar activation of Akt in energy-restricted rodents [22,65], this result should have impacted mTORC1 signaling pathways, and especially 4EBP1 and p70S6K.…”

“…J o u r n a l P r e -p r o o f 6 During the last decade, several experimental models have been developed, essentially in rodents, to better understand the cellular mechanisms involved in sarcopenia related to malnutrition. Some of these rodent models reproduce the hypermetabolism related to chronic diseases [20,21], others induce a drastic protein-energy restriction to mimic marasmus or kwashiorkor [22,23]. Though, the rodent models present several limitations related to their phylogenetic distance and significant differences compared to humans in terms of eating behavior, circadian rhythm and general anatomy.…”

A novel oral nutritional supplement improves gait speed and mitochondrial functioning compared to standard care in older adults with (or at risk of) undernutrition: results from a randomized controlled trial

“…Results of the stimulation of PBMCs with memory recall mixes did not suggest any substantial changes in immune function on both groups, although the increased proportion of T and B cells in the novel supplement group may impact the general immune status of the subjects. Of note, the same novel supplement seemed to increase the expression of immune-protective pathways in mice [21]. The study reported in this paper is one of the larger randomized controlled trials with ONS run in community-dwelling participants with (risk of) undernutrition.…”

“…Hence, we set out to test a novel whey-based ONS, high in leucine and vitamin D that previously was found to provide additional benefits [19,20] and reinforced with UA that may affect muscle metabolism [17]. This novel ONS was tested in a calorically restricted mouse model and found to preserve muscle mass while affecting regulatory pathways [21]. In this study, we compared the effects of this novel supplement with a standard supplement on body composition, physical functioning, blood markers, and skeletal muscle gene and protein expression in older adults with (or at risk of) undernutrition without changing their activity pattern and without additional exercise.…”

Screening for Sarcopenia (Physical Frailty) in the COVID-19 Era

“…Loss of muscle mass and associated muscle weakness can be reverted, especially during early stages, through sound exercise and nutritional interventions [19,[63][64][65][66][67][68][69]. Evidence from animal studies shows that nutritional interventions for muscle wasting yield better results when administered early during the development of muscle atrophy [7,70]. erefore, proper screening and management of sarcopenia may support efforts aimed to slow or reverse the progression of physical frailty in old seniors [1].…”