Biology subjects

De Vadder, F.

Publications and source records attributed to De Vadder, F..

6 recordsLinked to original sources

bioRxiv2026

OrganScaleR: An Open Shiny Tool for Principled Organ-Weight Inference in Mouse Physiology

BackgroundOrgan weights are often divided by body weight to report "relative" organ size. Yet ratios usually stay size-dependent and become misleading. We built a simple decision path for size adjustment and wrapped it in a Shiny application so physiologists can get correct answers without coding. MethodsWe reused liver and body-weight data from a mouse nutrition study for confirmatory examples in two common cases: when diet groups shared a wide body-size range, and when diet produced much smaller animals with little overlap. We compared liver-to-body-weight ratios with size-adjusted regression when the body-size overlap allowed comparisons, and with causal Bayesian mediation when it did not. The full workflow was implemented in OrganScaleR, a guided R Shiny application. ResultsThe ratio-normalized organ weight is still associated with body weight, leading to misleading comparisons. Modeling liver weight against body weight gave more cautious, size-adjusted effects when groups shared a common size range. When diets shifted body size strongly and overlap was limited, causal mediation showed that most organ differences followed the change in body weight rather than an organ-specific action. Simulations confirmed that ratios can generate false positives and biased estimates under allometric scaling, while model-based approaches remained reliable. OrganScaleR implements this decision workflow in a guided Shiny application that returns interpretable effects. ConclusionsOrganScaleR selects scale, enforces common support, and routes the analysis to size-adjusted ANCOVA or causal Bayesian mediation depending on body-weight overlap. It reports adjusted effects in original units through a point-and-click workflow, removing the statistical barrier to abandoning ratio normalization. HighlightsO_LIBody-weight ratios remain size-dependent and distort organ-weight comparisons. C_LIO_LIANCOVA at a common reference body weight removes ratio bias when groups overlap. C_LIO_LICausal mediation separates organ-specific from body-weight-mediated diet effects. C_LIO_LISimulations confirm ratios inflate false-positive rates under allometric scaling. C_LIO_LIOrganScaleR guides size adjustment without coding via a point-and-click workflow. C_LI

physiology↗

bioRxiv2025

Liver FGF21 mediates sex-specific adaptation to juvenile protein malnutrition

Dietary protein sufficiency during childhood is essential for healthy growth and tissue development. Chronic protein deficiency leads to stunting, height-for-age more than two standard deviations below the median, and affects 149 million children under five (https://www.who.int/publications/i/item/9789240073791). Linear growth is governed by the somatotropic axis, wherein pituitary growth hormone (GH) stimulates hepatic insulin-like growth factor 1 (IGF-1) to promote bone elongation1. Although boys are consistently more stunted than girls across populations (ranging from 18% to 45%)2,3, mechanisms underlying this apparent resilience remain unclear. Rodent studies suggest that the protein-to-carbohydrate ratio modulates life-history traits such as metabolism, lifespan, and reproduction, with evidence of sex-dependent sensitivity4,5. Whether such dimorphism reflects coordinated developmental adaptations in response to protein scarcity, particularly in females, has not been fully explored. Here, we show that juvenile dietary protein restriction causes sexually dimorphic adaptations with pronounced stunting in males and delayed reproductive maturation in females. Using liver-specific deletion, we identify fibroblast growth factor 21 (FGF21) as a sex-specific hepatic regulator of female somatic growth and reproductive development, revealing a dimorphic endocrine adaptation to early-life protein scarcity. Our findings position FGF21 as a critical physiological checkpoint coordinating growth and reproductive timing in response to nutritional stress.

physiology↗

bioRxiv2024

Protein restriction associated with high fat induces metabolic dysregulation without obesity in juvenile mice

Dysregulation of energy metabolism, including hyperglycemia, insulin resistance and fatty liver have been reported in a substantial proportion of lean children. However, non-obese murine models recapitulating these features are lacking to study the mechanisms underlying the development of metabolic dysregulations in lean children. Here, we develop a model of diet-induced metabolic dysfunction without obesity in juvenile mice by feeding male and female mice a diet reflecting Western nutritional intake combined with protein restriction (mWD) during 5 weeks after weaning. mWD-fed mice (33% fat, 8% protein) do not exhibit significant weight gain and have moderate increase in adiposity compared to control mice (16% fat, 20% protein). After 3 weeks of mWD, juvenile mice have impaired glucose metabolism including hyperglycemia, insulin resistance and glucose intolerance. mWD also triggers hepatic metabolism alterations, as shown by the development of simple liver steatosis. Both male and female mice fed with mWD displayed metabolic dysregulation, which a probiotic treatment with Lactiplantibacillus plantarum WJL failed to improve. Overall, mWD-fed mice appear to be a good preclinical model to study the development of diet-induced metabolic dysfunction without obesity in juveniles.

physiology↗

bioRxiv2024

Semaglutide interferes with postnatal growth in a diet-dependent manner

GLP-1 receptor agonists, including semaglutide, are increasingly used to treat obesity--and to a lesser extent, type 2 diabetes--in children and adolescents. Despite their therapeutic promise, the impact of semaglutide on key endocrine and metabolic developmental processes during this period is not yet fully understood. To address the limited understanding of GLP-1 receptor agonists during development, we investigated the effects of chronic semaglutide treatment on growth and metabolism of weanling male mice. In juvenile mice displaying a normal growth pattern, semaglutide lowered blood glucose without affecting food intake or weight gain. In contrast, chronic semaglutide treatment in growth-stunted juveniles exacerbated linear growth impairment, despite preserving glucose-lowering effects. Transcriptomic analysis of the liver, complemented by gene expression studies in other metabolically active tissues, suggested altered energy expenditure, indicating a complex interaction between semaglutide, energy metabolism, and growth during juvenile development. These findings underscore the importance of developmental context when evaluating the safety and efficacy of GLP-1 receptor agonists in pediatric populations.

physiology↗

bioRxiv2024

Suboptimal refeeding compensates stunting in a mouse model of juvenile malnutrition

BackgroundEarly life, particularly after weaning, is the most rapid period of growth in mammals, and this growth is highly dependent on adequate nutrition. Protein-energy malnutrition (PEM) during this critical window can lead to stunting and wasting, which have long-term health consequences. ObjectiveThis study aimed to develop a mouse model of juvenile PEM to assess the effects of refeeding with various diets and interventions on growth recovery, including the impact of probiotic supplementation and suboptimal refeeding diets. MethodsJuvenile C57Bl/6J mice were fed a low-protein diet (LPD, 5% kcal from protein) starting at postnatal day 14 (P14) to induce malnutrition. Following weaning, both male and female mice were refed an optimal diet (Altromin 1310, 27% kcal from protein) at different times ranging from P28 to P56. In a second intervention, male mice were supplemented during refeeding with Lactiplantibacillus plantarum WJL (LpWJL), a probiotic known to stimulate growth in malnourished conditions. A final group of malnourished male mice were refed with a Western diet (WD, 34.5% kcal from fat; 15.3% kcal from protein) or a modified Western diet (MWD, 34.2% kcal from fat; 7.5% kcal from protein) to model suboptimal refeeding. ResultsRefeeding with an optimal diet fully restored growth in female mice, but male mice exhibited persistent stunting despite nutritional rehabilitation. LpWJL treatment during refeeding did not enhance systemic growth in males. In contrast, refeeding with WD or MWD restored body length but impaired glucose metabolism, particularly in mice refed MWD after PEM. LpWJL exacerbated glucose intolerance in the suboptimal refeeding groups. ConclusionSex-dependent differences exist in the recovery from early-life malnutrition, with males showing incomplete growth recovery despite optimal refeeding. Suboptimal diets, while compensating for stunting, impair glucose metabolism, especially when protein intake is insufficient. Probiotic supplementation with LpWJL did not improve growth outcomes.

physiology↗

bioRxiv2019

A standardized gnotobiotic mouse model harboring a minimal 15-member mouse gut microbiota recapitulates SOPF phenotype

Mus musculus is the classic mammalian model for biomedical research. Despite global efforts to standardize breeding and experimental procedures, the undefined composition and interindividual diversity of the microbiota of laboratory mice remains a limitation. In an attempt to standardize the gut microbiome in preclinical mouse studies, we developed a simplified mouse microbiota composed of 15 strains from 7 of the 20 most prevalent bacterial families representative of the fecal microbiota of C57BL/6J Specific (and Opportunistic) Pathogen-Free (SPF/SOPF) animals and derived a new standardized gnotobiotic mouse model called GM15. GM15 recapitulates extensively the functionalities found in the C57BL/6J SOPF microbiota metagenome, and GM15 animals are phenotypically similar to SOPF or SPF animals in two different facilities. They are also less sensitive to the deleterious effects of post-weaning malnutrition. The GM15 model provides increased reproducibility and robustness of preclinical studies by limiting the confounding effect of fluctuation in microbiota composition, and offers new opportunities for research focused on how the microbiota shapes host physiology in health and disease.

microbiology↗