Proteolysis inhibition by hibernating bear serum leads to increased protein content in human muscle cells

Muscle atrophy is one of the main characteristics of human ageing and physical inactivity, with resulting adverse health outcomes. To date, there are still no efficient therapeutic strategies for its prevention and/or treatment. However, during hibernation, bears exhibit a unique ability for preserving muscle in conditions where muscle atrophy would be expected in humans. Therefore, our objective was to determine whether there are components of bear serum which can control protein balance in human muscles. In this study, we exposed cultured human differentiated muscle cells to bear serum collected during winter and summer periods, and measured the impact on cell protein content and turnover. In addition, we explored the signalling pathways that control rates of protein synthesis and degradation. We show that the protein turnover of human myotubes is reduced when incubated with winter bear serum, with a dramatic inhibition of proteolysis involving both proteasomal and lysosomal systems, and resulting in an increase in muscle cell protein content. By modulating intracellular signalling pathways and inducing a protein sparing phenotype in human muscle cells, winter bear serum therefore holds potential for developing new tools to fight human muscle atrophy and related metabolic disorders

18th Euro Fed Lipid Congress and Expo

International audienceDietary synthetic emulsifiers have recently been shown to promote metabolic syndrome and alter the gut microbiota. The effects of natural emulsifiers, such as vegetable lecithin, remain poorly described. Our objective was to evaluate, in mice, the impact of soy and rapeseed lecithin (SL and RL), both rich in essential α-linolenic acid (ALA), on HFD-induced adiposity, inflammation and the gut microbiota. For 13 weeks, male Swiss mice (n=72) were fed a Chow diet, a HFD devoid of ALA, or different ALA-enriched HFD (identical ALA content: 4.7%) containing 0% lecithin (HF-0L), a nutritional dose (10%) of SL or RL (HF-10SL, HF-10RL) or a supplemental dose of RL (20%; HF-20RL). Biometric parameters and the epididymal adipose tissue (EAT) were analysed; hepatic lipid composition was determined by GC-FID, gene expression by RT-qPCR, and faecal microbiota composition by 16S sequencing. In all groups fed ALA-rich diets, the proportion of ALA in both liver triacylglycerols and phospholipids was increased, but the vectorisation of ALA as lecithin did not further increase its hepatic bioavailability, compared to an oil (HF-0L). The incorporation of 10% SL, but not RL, in ALA-enriched HFD significantly increased weight gain (p<0.001) and adiposity (p<0.001) vs Chow. Both HFD and HF-10SL induced increased expression of genes of macrophage infiltration in the EAT (ex. Tnfα, Cd11c) vs Chow (p<0.05), while HF-0L and RL induced levels of such inflammatory markers in-between Chow and HFD. Finally, HF-10RL reduced HFD-induced loss of α-diversity of the gut microbiota and altered the abundance of several bacterial groups, such as Desulfovibrionaceae. All in all, the addition of lecithins to HFD did not exacerbate HFD-inflammation and RL increased gut bacterial diversity. This study hence illustrates the importance of considering certain natural emulsifiers, notably rapeseed lecithin, as alternatives to synthetic emulsifiers of known detrimental effects

Fibroblast growth factor 19 regulates skeletal muscle mass and ameliorates muscle wasting in mice

International audienceThe endocrine-derived hormone fibroblast growth factor (FGF) 19 has recently emerged as a potential target for treating metabolic disease(1). Given that skeletal muscle is a key metabolic organ, we explored the role of FGF19 in that tissue. Here we report a novel function of FGF19 in regulating skeletal muscle mass through enlargement of muscle fiber size, and in protecting muscle from atrophy. Treatment with FGF19 causes skeletal muscle hypertrophy in mice, while physiological and pharmacological doses of FGF19 substantially increase the size of human myotubes in vitro. These effects were not elicited by FGF21, a closely related endocrine FGF member. Both in vitro and in vivo, FGF19 stimulates the phosphorylation of the extracellular-signal-regulated protein kinase 1/2 (ERK1/2) and the ribosomal protein S6 kinase (S6K1), an mTOR-dependent master regulator of muscle cell growth. Moreover, mice with a skeletal-muscle-specific genetic deficiency of beta-Klotho (KLB), an obligate co-receptor for FGF15/19 (refs. 2,3), were unresponsive to the hypertrophic effect of FGF19. Finally, in mice, FGF19 ameliorates skeletal muscle atrophy induced by glucocorticoid treatment or obesity, as well as sarcopenia. Taken together, these findings provide evidence that the enterokine FGF19 is a novel factor in the regulation of skeletal muscle mass, and that it has therapeutic potential for the treatment of muscle wasting