Background In mammals, the hibernating state is characterized by biochemical adjustments, which include metabolic rate depression and a shift in the primary fuel oxidized from carbohydrates to lipids. A number of studies of hibernating species report an upregulation of the levels and/or activity of lipid oxidizing enzymes in muscles during torpor, with a concomitant downregulation for glycolytic enzymes. However, other studies provide contrasting data about the regulation of fuel utilization in skeletal muscles during hibernation. Bears hibernate with only moderate hypothermia but with a drop in metabolic rate down to ~ 25% of basal metabolism. To gain insights into how fuel metabolism is regulated in hibernating bear skeletal muscles, we examined the vastus lateralis proteome and other changes elicited in brown bears during hibernation. Results We show that bear muscle metabolic reorganization is in line with a suppression of ATP turnover. Regulation of muscle enzyme expression and activity, as well as of circulating metabolite profiles, highlighted a preference for lipid substrates during hibernation, although the data suggested that muscular lipid oxidation levels decreased due to metabolic rate depression. Our data also supported maintenance of muscle glycolysis that could be fuelled from liver gluconeogenesis and mobilization of muscle glycogen stores. During hibernation, our data also suggest that carbohydrate metabolism in bear muscle, as well as protein sparing, could be controlled, in part, by actions of n-3 polyunsaturated fatty acids like docosahexaenoic acid. Conclusions Our work shows that molecular mechanisms in hibernating bear skeletal muscle, which appear consistent with a hypometabolic state, likely contribute to energy and protein savings. Maintenance of glycolysis could help to sustain muscle functionality for situations such as an unexpected exit from hibernation that would require a rapid increase in ATP production for muscle contraction. The molecular data we report here for skeletal muscles of bears hibernating at near normal body temperature represent a signature of muscle preservation despite atrophying conditions. Electronic supplementary material The online version of this article (10.1186/s12983-019-0312-2) contains supplementary material, which is available to authorized users.

Of the hepatic cell lines developed for in vitro studies of hepatic functions as alternatives to primary human hepatocytes, many have lost major liver-like functions, but not HepaRG cells. The increasing use of the latter worldwide raises the need for establishing the reference functional status of early biobanked HepaRG cells. Using deep proteome and secretome analyses, the levels of master regulators of the hepatic phenotype and of the structural elements ensuring biliary polarity were found to be close to those in primary hepatocytes. HepaRG cells proved to be highly differentiated, with functional mitochondria, hepatokine secretion abilities, and an adequate response to insulin. Among differences between primary human hepatocytes and HepaRG cells, the factors that possibly support HepaRG transdifferentiation properties are discussed. The HepaRG cell system thus appears as a robust surrogate for primary hepatocytes, which is versatile enough to study not only xenobiotic detoxification, but also the control of hepatic energy metabolism, secretory function and disease-related mechanisms.

BackgroundLife history theories predict that investment in current reproduction comes at a cost for future reproduction and survival. Oxidative stress is one of the best documented mechanisms underlying costs of reproduction to date. However, other, yet to be described molecular mechanisms that play a short term role during reproduction may explain the negative relationships underlying the cost of reproduction. To identify such new mechanisms, we used a global proteomic determination of liver protein profiles in laboratory adult female mice whose litter size had been either reduced or enlarged after birth. This litter size manipulation was expected to affect females by either raising or decreasing their current reproductive effort. At the same time, global parameters and levels of oxidative stress were also measured in all females.ResultsBased on plasma analyses, females with enlarged litters exhibited increased levels of oxidative stress at the date of weaning compared to females with reduced litters, while no significant difference was found between both the latter groups and control females. None of the liver proteins related to oxidative balance were significantly affected by the experimental treatment. In contrast, the liver protein profiles of females with enlarged and reduced litters suggested that calcium metabolism and cell growth regulation were negatively affected by changes in the number of pup reared.ConclusionsPlasma oxidative stress levels in reproductive mice revealed that the degree of investment in reproduction can actually incur a cost in terms of plasmatic oxidative stress, their initial investment in reproduction being close to maximum and remaining at a same level when the energy demand of lactation is reduced. Liver proteomic profiles in reproductive females show that hepatic oxidative stress is unlikely to be involved in the cost of reproduction. Reproductive females rather exhibited liver protein profiles similar to those previously described in laboratory ageing mice, thus suggesting that hepatic cell pro-ageing processes may be involved in the cost of reproduction. Overall, our data illustrate how a proteomic approach can unravel new mechanisms sustaining life-history trade-offs, and reproduction costs in particular.