Dexamethasone plus glucagon-like peptide 2 given to lactating rat dams has a late effect on intestinal lipid uptake in the weanling offspring

Abstract

Background: Glucagon-like peptide 2 (GLP-2) has a trophic effect on the intestine and enhances intestinal absorption in adult animals, but its effect in young rats is unknown. Glucocorticosteroids accelerate the ontogeny of the intestine, and in adult animals they increase the uptake of sugars and lipids. We hypothesized that GLP-2 and dexamethasone (DEX), when administrated to lactating rat dams, will enhance lipid uptake in the suckling and weanling offspring.

Methods: Eight nursing rats were treated during lactation, 19 to 21 days, with GLP-2 (0.1 microg/g/d subcutaneously [s.c.]), DEX (0.128 microg/g/d s.c.), GLP-2 + DEX (GLP-2 0.1 microg/g/d s.c. plus DEX 0.128 microg/g/d s.c.), or placebo. Half of the offspring ("sucklings") were killed at 19 to 21 days of age, and half were killed 4 weeks later ("weanlings"). The rate of intestinal uptake of fatty acids (12:0, lauric; 16:0, palmitic; 18:0, stearic; 18:1, oleic; 18:2, linoleic; and 18:3, linolenic) and cholesterol were assessed using an in vitro ring technique.

Results: GLP-2 and DEX resulted in loss of body weight in sucklings, which was prevented by giving the combination GLP-2 + DEX. The jejunal atrophy in sucklings given DEX was prevented by giving GLP-2 + DEX, but GLP-2 + DEX did not prevent the decline in jejunal and ileal villous height and crypt depth observed in weanlings given DEX. GLP-2 had little effect on lipid uptake in sucklings, whereas DEX or GLP-2 + DEX increased the uptake of lipids. In contrast, in weanlings there was malabsorption of several lipids with GLP-2 or GLP-2 + DEX, but not with DEX. Lipid uptake was lower in weanlings than in sucklings, and this age-associated decline was not altered by GLP-2 or DEX.

Conclusions: The loss of body weight and the jejunal atrophy induced by DEX in sucklings is prevented by adding GLP-2. Giving DEX or GLP-2 + DEX to lactating mothers enhances lipid uptake in their suckling offspring. In marked contrast, a month after lactating dams were given GLP-2 or GLP-2 + DEX, there was reduced lipid absorption in the postweaning animals. Thus, giving GLP-2 + DEX during lactation may be useful to enhance lipid uptake in the suckling offspring, without adverse effects on body weight or intestinal characteristics. However, the late effects of this treatment on lipid absorption were of concern, and could be potentially deleterious to the nutritional well-being of the animal.