Biology subjects

Alameddine, M.

Publications and source records attributed to Alameddine, M..

5 recordsLinked to original sources

bioRxiv2023

Lifelong dietary protein restriction accelerates skeletal muscle loss and reduces muscle fibre size by impairing proteostasis and mitochondrial homeostasis

The early life environment significantly affects the development of age-related skeletal muscle disorders. However, the long-term effects of lactational protein restriction on skeletal muscle are still poorly defined. Our study revealed that male mice nursed by dams fed a low-protein diet during lactation exhibited skeletal muscle growth restriction. This was associated with a dysregulation in the expression levels of genes related to the ribosome, mitochondria and skeletal muscle development. We reported that lifelong protein restriction accelerated loss of type-IIa muscle fibres and reduced muscle fibre size by impairing mitochondrial homeostasis and proteostasis at 18 months of age. However, feeding a normal-protein diet following lactational protein restriction prevented accelerated fibre loss and fibre size reduction in later life. These findings provide novel insight into the mechanisms by which lactational protein restriction hinders skeletal muscle growth and includes evidence that lifelong dietary protein restriction accelerated skeletal muscle loss in later life.

physiology↗

bioRxiv2023

The effect of lactational low protein diet on skeletal muscle during adulthood and ageing in male and female mouse offspring

Sarcopenia is characterised by loss of skeletal muscle mass and function associated with a reduction in muscle fibres. External factors, like exercise and diet, can also influence skeletal muscle mass and contribute to muscle fibre loss. Maternal programming refers to the effect of maternal environmental factors such as nutrition that lead to phenotypic changes in the offspring. Maternal malnutrition has been linked to a reduction in body weight and impaired development of skeletal muscle of the offspring; however, there are no studies that reported the long-term effect of maternal low protein diet on the ageing of skeletal muscles. This study aimed to examine how maternal protein deficiency during lactation affects skeletal muscle development and ageing in the offspring. Pups born from normally fed mothers were lactated by low protein fed mothers. Post-weaning, mice were either maintained on a low protein diet (LPD) or switched to normal protein diet (NPD). Pups born from normally fed mothers and maintained on NPD during lactation and afterwards were used as control. In males, the diet mainly affected the size of the myofibres without major effect on fibre number and led to a reduced grip strength of ageing mice (24 months). Female mice had a lower body and muscle weight at weaning but caught up with control mice at 3 months. During ageing, muscle weight, myofibre number and survival rate of female pups were significantly affected. These findings highlight longitudinal animal research for nutritional programming and the importance of sexual dimorphism in response to challenges. HighlightsO_LIPostnatal low protein diet significantly decreases the survival rate of female but not male mice. C_LIO_LIDuring ageing, female mice fed a low protein diet during lactation have lower muscle weight. C_LIO_LIDuring ageing, female mice fed a low protein diet postnatally maintain their myofibre number. C_LIO_LIMale mice fed a low protein diet postnatally have lower body weight and muscle weight throughout their lifespan. C_LIO_LILow protein diet affects myofibres size of TA muscle of male but not female mice at 3 months of age however this effect is lost during ageing. C_LI

physiology↗

bioRxiv2022

Postnatal protein intake as a determinant of skeletal muscle structure and function in mice - a pilot study

Sarcopenia is characterised by an age-related decrease in the number of muscle fibres and additional weakening of the remaining fibres, resulting in a reduction in muscle mass and function. Many studies associate poor maternal nutrition during gestation and/or lactation with altered skeletal muscle homeostasis in the offspring and the development of sarcopenia. The aim of this study was to determine whether the musculoskeletal physiology in offspring born to mouse dams fed a low-protein diet during pregnancy was altered and whether any physiological changes could be modulated by the nutritional protein content in early postnatal stages. Thy1-YFP female mice were fed ad libitum on either a normal (20%) or a low-protein (5%) diet. Newborn pups were cross-fostered to different lactating dams (maintained on 20% or 5% diet) to generate 3 groups analysed at weaning (21 days): Normal-to-Normal (NN), Normal-to-Low (NL) and Low-to-Normal (LN). Further offspring were maintained ad libitum on the same diet as during lactation until 12 weeks of age creating another 3 groups (NNN, NLL, LNN). Mice on a low protein diet postnatally (NL, NLL) exhibited a significant reduction in body and muscle weight persisting up to 12 weeks, unlike mice on a low protein diet only prenatally (LN, LNN). Muscle fibre size was reduced in mice from the NL but not LN group, showing recovery at 12 weeks of age. Muscle force was reduced in NLL mice, concomitant with changes in the NMJ site and changes in atrophy-related and myosin genes. In addition, CT scans of mouse tibiae at 12 weeks of age revealed changes in bone mass and morphology, resulting in a higher bone mass in the NLL group than the control NNN group. Finally, changes in the expression of miR-133 in the muscle of NLL mice suggest a regulatory role for this microRNA in muscle development in response to postnatal diet changes. Overall, this data shows that a low maternal protein diet and early postnatal life low-protein intake in mice can impact skeletal muscle physiology and function in early life while postnatal low protein diet favors bone integrity in adulthood.

physiology↗

bioRxiv2021

Small-RNA sequencing reveals altered skeletal muscle microRNAs and snoRNAs signatures in weanling male offspring from mouse dams fed a low protein diet during lactation

Nutrition plays a key role in pre- and postnatal growth of the musculoskeletal system. Maternal diet during gestation and lactation affects the development of skeletal muscles in the offspring and determines muscle health in later life, however, the molecular mechanisms that govern these effects are largely unknown. In this study, we aim to describe the association between maternal low protein diet-induced changes in offspring skeletal muscle and the differential expression (DE) of small non-coding RNAs (sncRNAs). We used a mouse model of maternal protein restriction to characterise the impact of early-life undernutrition on skeletal muscle morphology in male offspring at weaning. Mouse dams were fed either a normal (N, 20%) or a low protein (L, 8%) diet during gestation and newborn pups were cross-fostered to N or L lactating dams, resulting in the generation of NN, NL and LN offspring groups. Total body and tibialis anterior (TA) weights were decreased in NL males but not different in the LN group, as compared to NN, although neonates from low protein fed dams were smaller at birth than those born to dams fed a normal protein. However, histological evaluation of TA muscle revealed reduced muscle fibre size in both groups at the end of lactation. Small RNA-seq analysis demonstrated DE of multiple classes of sncRNAs, including miRs, snoRNAs and snRNAs. Bioinformatic analyses of miRs-15a, -34a, -122 and -199a, in combination with known myomiRs, confirmed their implication in key muscle-specific biological processes and cellular functions and suggest a promising set of miRs in muscle physiology studies. To our knowledge, this is the first comprehensive report for the DE of sncRNAs in nutrition-associated programming of skeletal muscle development, highlighting the need for further research.

molecular biology↗

bioRxiv2020

Low protein intake compromises the recovery of lactation-induced bone loss in female mouse dams without affecting skeletal muscles.

ABSTRACTLactation-induced bone loss occurs due to high calcium requirements for fetal growth but skeletal recovery is normally achieved promptly post-weaning. Dietary protein is vital for fetus and mother but the effects of protein undernutrition on the maternal skeleton and skeletal muscles is largely unknown. We used mouse dams fed with normal (N, 20%) or low (L, 8%) protein diet during gestation and lactation and maintained on the same diets (NN, LL) or switched from low to normal (LN) during a 28d skeletal restoration period post lactation. Skeletal muscle morphology and neuromuscular junction integrity was not different between any of the groups. However, dams fed the low protein diet showed extensive bone loss by the end of lactation, followed by full skeletal recovery in NN dams, partial recovery in LN and poor bone recovery in LL dams. Primary osteoblasts from low protein diet fed mice showed decreased in vitro bone formation and decreased osteogenic marker gene expression; promoter methylation analysis by pyrosequencing showed no differences in Bmpr1a, Ptch1, Sirt1, Osx and Igf1r osteoregulators, while miR-26a, -34a and -125b expression was found altered in low protein fed mice. Therefore, normal protein diet is indispensable for maternal musculoskeletal health during the reproductive period.Competing Interest StatementThe authors have declared no competing interest.View Full Text

physiology↗