Validation of a Feed Protocol in a Mouse Model That Mimics Marasmic Malnutrition

Abstract

Host nutritional status directly interferes with immunity and/or susceptibility to infectious diseases. To understand the mechanisms behind this relationship, the use of animal models and feeding protocols is necessary. In the literature, studies reporting marasmic malnutrition in mice are not common. In this context, the objective of this study was to validate a feed methodology that mimics marasmic malnutrition, examining the nutritional, biochemical, and hematological status in BALB/c mice. Weaned BALB/c mice were or were not fed a Restricted diet (36.26% carbohydrate, 8.79% protein, 4.95% fat, and 7.62 kJ/100 g). Some malnourished mice underwent a refed process with a Control diet (65.93% carbohydrate, 24.18% protein, 9.89% fat, and 15.24 kJ/100 g). The nutritional status of the mice was evaluated through phenotypic markers and hematological and biochemical parameters. Our results showed that the Restricted diet was able to induce mild malnutrition in mice, resulting in mouse weight loss of 12%, which could be reversed after refeeding. Malnourished mice demonstrated slow body growth and low body mass index (BMI) values. Malnourished mice also showed physical and behavioral changes, a reduction of 47.5% in leukocyte counts and a 2-fold increase in cholesterol levels. In conclusion, our feeding protocol was able to generate mild malnutrition and cause changes in the nutritional status of mice that could be similar to those observed in marasmic malnutrition.

Suboptimal refeeding compensates stunting in a mouse model of juvenile malnutrition

“…While this results in a severe phenotype regarding growth and weight, our mice did not show any particular sign of torpor, reduced activity, or change in appetite during the nutritional challenge. Moreover, unlike Ferreira-Paes et al (21), who describe a model of marasmus using weanling BALB/c mice, nutritional rehabilitation in male mice did not fully resolve the severity of protein malnutrition. Indeed, in our experimental setting, male mice were stunted after nutritional rehabilitation, although early-life wasting was corrected.…”

“…However, it does not exhibit classic traits of kwashiorkor such as edema and hepatomegaly (31), probably due to the fact that our mice are not in contact with any enteric pathogens and thus are not susceptible to infection and inflammation. Indeed, several studies have shown that malnourished mice are more susceptible to infection, thus mimicking one of the hallmarks of human malnutrition (20,21). Furthermore, nutritional rehabilitation after kwashiorkor results in increased IGF-1 levels, but the values are lower than in healthy children (32).…”

“…We first investigated how relevant our model of malnutrition was to human disease. Indeed, although several models have been published (20,21), there is no standard murine model of PEM. We first characterized the impact on weight gain and linear growth in C57Bl/6J mice fed an LPD, starting at P14 and going on after weaning (which took place at P21).…”

Protein Malnutrition in BALB/c Mice: An Experimental Model Resembling Clinical Scenario

“…In the clinical scenario, impaired liver function leads to altered biochemical parameters in marasmus protein malnutrition. 19 Literature also indicates that the increase in Kupffer cells results from malnutrition. 36 Considering this evidence, our study confirms that the developed mice model is stable and clinically relevant.…”

“…[16][17][18] Recently, a study using a low protein diet (LPD) was validated. 19 The validated diet was used for a concise period of observation and would not resemble the clinical condition where the exposure is chronic/ continuous.…”