Dystropathology increases energy expenditure and protein turnover in the mdx mouse model of Duchenne muscular dystrophy

The skeletal muscles in Duchenne muscular dystrophy and the mdx mouse model lack functional dystrophin and undergo repeated bouts of necrosis, regeneration, and growth. These processes have a high metabolic cost. However, the consequences for whole body energy and protein metabolism, and on the dietary requirements for these macronutrients at different stages of the disease, are not well-understood. This study used juvenile (4- to 5- wk-old) and adult (12- to 14-wk-old) male dystrophic C57BL/10ScSn-mdx/J and age-matched C57BL/10ScSn/J control male mice to measure total and resting energy expenditure, food intake, spontaneous activity, body composition, whole body protein turnover, and muscle protein synthesis rates. In juvenile mdx mice that have extensive muscle damage, energy expenditure, muscle protein synthesis, and whole body protein turnover rates were higher than in age-matched controls. Adaptations in food intake and decreased activity were insufficient to meet the increased energy and protein needs of juvenile mdx mice and resulted in stunted growth. In (non-growing) adult mdx mice with less severe dystropathology, energy expenditure, muscle protein synthesis, and whole body protein turnover rates were also higher than in age-matched controls. Food intake was sufficient to meet their protein and energy needs, but insufficient to result in fat deposition. These data show that dystropathology impacts the protein and energy needs of mdx mice and that tailored dietary interventions are necessary to redress this imbalance. If not met, the resultant imbalance blunts growth, and may limit the benefits of therapies designed to protect and repair dystrophic muscles

Anthropometry‐based prediction of body composition in early infancy compared to air‐displacement plethysmography

Funder: Danone Nutricia ResearchFunder: EU Commission for JPI HDHL program ‘Call III Biomarkers’ for project: BioFN ‐ Biomarkers for Infant Fat Mass Development and Nutrition; Grant(s): 696295Summary: Background: Anthropometry‐based equations are commonly used to estimate infant body composition. However, existing equations were designed for newborns or adolescents. We aimed to (a) derive new prediction equations in infancy against air‐displacement plethysmography (ADP‐PEA Pod) as the criterion, (b) validate the newly developed equations in an independent infant cohort and (c) compare them with published equations (Slaughter‐1988, Aris‐2013, Catalano‐1995). Methods: Cambridge Baby Growth Study (CBGS), UK, had anthropometry data at 6 weeks (N = 55) and 3 months (N = 64), including skinfold thicknesses (SFT) at four sites (triceps, subscapular, quadriceps and flank) and ADP‐derived total body fat mass (FM) and fat‐free mass (FFM). Prediction equations for FM and FFM were developed in CBGS using linear regression models and were validated in Sophia Pluto cohort, the Netherlands, (N = 571 and N = 447 aged 3 and 6 months, respectively) using Bland–Altman analyses to assess bias and 95% limits of agreement (LOA). Results: CBGS equations consisted of sex, age, weight, length and SFT from three sites and explained 65% of the variance in FM and 79% in FFM. In Sophia Pluto, these equations showed smaller mean bias than the three published equations in estimating FM: mean bias (LOA) 0.008 (−0.489, 0.505) kg at 3 months and 0.084 (−0.545, 0.713) kg at 6 months. Mean bias in estimating FFM was 0.099 (−0.394, 0.592) kg at 3 months and −0.021 (−0.663, 0.621) kg at 6 months. Conclusions: CBGS prediction equations for infant FM and FFM showed better validity in an independent cohort at ages 3 and 6 months than existing equations

Undernutrition during suckling in rats elevates plasma adiponectin and its receptor in skeletal muscle regardless of diet composition : a protective effect?

Objective:Nutrition during critical periods in early life may increase the subsequent risk of obesity, hypertension and metabolic diseases in adulthood. Few studies have focused on the long-term consequences of poor nutrition during the suckling period on the susceptibility to developing obesity when exposed to a palatable cafeteria-style high-fat diet (CD) after weaning.Design:This study examined the impact of early undernutrition, followed by CD exposure, on blood pressure, hormones and genes important for insulin sensitivity and metabolism and skeletal muscle mRNA expression of adiponectin receptor 1 (AdipoR1), carnitine palmitoyl-transferase I (CPT-1), cytochrome c oxidase 4 (COX4) and peroxisome proliferator-activated receptor alpha (PPARalpha). Following normal gestation, Sprague&ndash;Dawley rat litters were adjusted to 18 (undernourished) or 12 (control) pups. Rats were weaned (day 21) onto either palatable CD or standard chow.Results:Early undernourished rats were significantly lighter than control by 17 days, persisting into adulthood only when animals were fed chow after weaning. Regardless of litter size, rats fed CD had doubled fat mass at 15 weeks of age, and significant elevations in plasma leptin, insulin and adiponectin. Importantly, undernutrition confined to the suckling period, elevated circulating adiponectin regardless of post-weaning diet. Blood pressure was reduced in early undernourished rats fed chow, and increased by CD. Early undernutrition was associated with long-term elevations in the expression of AdipoR1, CPT-1, COX4 and PPARalpha in skeletal muscle.Conclusion:This study demonstrates the important role of early nutrition on body weight and metabolism, suggesting early undernourishment enhances insulin sensitivity and fatty-acid oxidation. The long-term potential benefit of limiting nutrition in the early postnatal period warrants further investigation.<br /