Apolipoprotein E knockout mice have accentuated malnutrition with mucosal disruption and blunted insulin-like growth factor I responses to refeeding

Abstract

Apolipoprotein E (apoE) is synthesized mainly in the liver and in the brain and is critical for cholesterol metabolism and recovery from brain injury. However, although apoE mRNA increases at birth, during suckling, and after fasting in rat liver, little is known about its role in early postnatal development. Using an established postnatal malnutrition model and apoE knock-out (ko) mice, we examined the role of apoE in intestinal adaptation responses to early postnatal malnutrition. Wild-type and apoE-ko mice were separated from their lactating dams for defined periods each day (4 hours on day 1, 8 hours on day 2, and 12 hours thereafter). We found significant growth deficits, as measured by weight gain or tail length, in the apoE-ko mice submitted to a malnutrition challenge, as compared with malnourished wild type, especially during the second week of postnatal development (P < .05). In addition, apoE-ko animals failed to show growth catch-up after refeeding, compared with wild-type malnourished controls. Furthermore, we found shorter crypts and reduced villus height and area in the apoE-ko malnourished mice, compared with controls, after refeeding. Insulinlike growth factor 1 expression was also blunted in the ileum in apoE-ko mice after refeeding, compared with wild-type controls, which exhibited full insulinlike growth factor 1 expression along the intestinal crypts, villi, and in the muscular layer. Taken together, these findings suggest the importance of apoE in coping with a malnutrition challenge and during the intestinal adaptation after refeeding. NIH Public Access

Arginine decreases Cryptosporidium parvum infection in undernourished suckling mice involving nitric oxide synthase and arginase

“…As previously described [15], the undernourished non-infected mice showed profound crypt derangement and shortening, with almost complete mitotic blunting. Rarely Paneth and goblet cells were found within the crypt.…”

“…In an earlier study, we demonstrated that undernutrition caused by breastfeeding restriction during the suckling time in rodents could lead to severe stunting, poor weight gain [15] and much heavier cryptosporidial infections [10]. In the current study, we have evaluated the potential benefit of the conditional amino acid L-arginine during intestinal adaptations against C. parvum infection in suckling mice afflicted with early post-natal malnutrition.…”

“…Their first day of life was recorded as post-natal day (D)1. Half of the offspring was separated from their lactating dam for increasing intervals starting on D4 of life, as described previously [14,15]; four hours at D4, eight hours at D5 and then twelve hours from D6 until D13. Separated pups were kept in an incubator box under controlled temperature (28 ± 2C).…”

Apolipoprotein E COG 133 mimetic peptide improves 5-fluorouracil-induced intestinal mucositis

“…This may be caused by a disrupted growth factor signaling, since we had shown impaired intestinal adaptations during catch-up growth following re-feeding in severe undernourished ApoE knock-out mice, with poor intestinal IGF-1 expression [21]. …”

Malnutrition as an enteric infectious disease with long-term effects on child development

“…Most strikingly, the ApoEko malnourished mice fail to repair mucosal damage or recover from their growth faltering following refeeding, thus showing they have dramatically reduced intestinal adaptive responses. This appeared to be due, at least in part, to blunted IGF‐I expression 145 …”