Treatment of suckling rats with GLP-2 plus dexamethasone increases the ileal uptake of fatty acids in later life

Glucocorticosteroids such as dexamethasone (Dex) increase sugar and lipid uptake in adult animals and accelerate the development of the immature intestine. The effect of Dex on the ontogeny of lipid absorption is unknown. In adult rats, glucagon-like peptide-2 (GLP-2) has a trophic effect on the intestine and enhances nutrient absorption. This study was undertaken to determine the effect of GLP-2 and Dex on the intestine uptake of lipids in suckling rats and to determine whether any such effect persists into the postweanling period. Sixty-four suckling rats were randomized into four groups. They were treated from days 11 to 21 with GLP-2 (0.1 mug.g(-1).day(-1) sc), Dex (0.128 mug.g(-1).day(-1) sc), GLP-2 plus Dex (GLP-2 0.1 mug.g(-1).day(-1) sc + Dex 0.128 mug.g(-1).day(-1) sc), or placebo. One-half the pups were killed at days 19-21 ("sucklings"), and one-half were killed 4 wk later ("weanlings"). The rate of intestinal uptake of six fatty acids (12: 0, lauric; 16: 0, palmitic; 18: 0, stearic; 18: 1, oleic; 18: 2, linoleic; and 18: 3, linolenic) and cholesterol was assessed using an in vitro ring technique. GLP-2 had no effect on lipid uptake. Dex increased the uptake of 18: 3 in sucklings, and the ileal uptake of 18: 0 was increased in weanlings. The combination of GLP-2 plus Dex had no effect in sucklings and increased the ileal uptake of 12: 0, 18: 0, 18: 1, 18: 2, and 18: 3 in weanlings. The enhanced uptake of fatty acids with GLP-2 plus Dex was not explained by alterations in the animals' body or intestinal weights, intestinal morphology, or intestinal- or liver-fatty acid binding proteins. Unlike adults, GLP-2 does not enhance lipid uptake in sucklings. Dex has a modest enhancing effect on selected fatty acid uptake both in sucklings as well as weanlings. GLP-2 plus Dex has an enhancing effect on the ileal uptake of fatty acids in weanlings 4 wk after their previous injection with GLP-2 plus Dex. It remains to be established what is the nutritional importance of this late effect of prior exposure to Dex or GLP-2 plus Dex on the intestinal uptake of lipids.