ABSTRACT: Glucagon-like peptide-2 (GLP-2) enhances intesti- nal growth and absorption in mature animals, and glucocortico- steroids (GC) increase the sugar and lipid uptake in adult animals. However, the role of GC and GLP-2 in the ontogeny of lipid ab- sorption is unknown. We hypothesized that GLP-2 and the GC dexamethasone (DEX), when administrated to rat dams during pregnancy and lactation, would enhance lipid uptake in the off- spring. Rat dams were treated in the last 10 d of pregnancy and during lactation with GLP-2 [0.1 μg/g/d subcutaneous (sc)], DEX (0.128 μg/g/d sc), GLP-2 + DEX, or a placebo. Sucklings were sac- rificed at 19–21 d of age, and weanlings were sacrificed 4 wk later. Lipid uptake was assessed using an in vitro ring uptake method. Although DEX and GLP-2 + DEX increased the jejunal mass, the jejunal lipid uptake was unchanged. In contrast, GLP-2, DEX, and GLP-2 + DEX reduced the ileal lipid uptake in suckling and weanling rats. This reduction was not due to alter- ations in intestinal morphology or to changes in fatty acid-bind- ing protein abundance, but it was partially explained by an in- crease in the effective resistance of the intestinal unstirred water layer. In sucklings, DEX dramatically reduced the jejunal lipid uptake to levels similar to those seen in weanlings, such that the normal ontogenic decline in lipid uptake was not observed. Giv- ing dams GLP-2 or DEX during pregnancy and lactation reduced lipid uptake in the offspring, and this persisted for at least 1 mon. The impact this may have on the nutritional well-being of the an- imal in later life is unknown. Paper no. L9663 in Lipids 40, 1141–1148 (November 2005). The ontogeny of the intestinal tract includes all the events in- volved in the development and maturation of the gut. This com- plex process involves morphological maturation with the tran- sition from the endodermal tube to the villous-crypt architec- ture and functional maturation of the digestive and absorptive functions, as well as the barrier properties of the mucosa (1–3). The digestive functions exhibit age-dependent alterations in the absorption of nutrients during the suckling and weanling pe- riod (4). These variations are due to alterations of abundance and/or activities of the transporters and digestive enzymes, as well as to changes in the permeability of the brush border mem- brane (BBM) (2,4–6). Intestinal lipid uptake involves both passive diffusion and protein-mediated transport (7). The uptake of lipids is higher in suckling rats than in adult rats, possibly because of their in- creased BBM permeability as well as the more efficient metab- olism of fat (8,9). The ontogeny of lipid absorption has not been studied extensively. Glucagon-like peptide-2 (GLP-2) en- hances the absorption of sugars in adult animals (10–12), but whether this peptide influences the intestinal absorption of lipids is not known. In adult rats, glucocorticosteroids (GC) in- crease the uptake of both sugars and lipids (13–15). GC may need to be given to pregnant and lactating mothers for health reasons, and it is not known whether this affects lipid absorp- tion in their offspring, whether any possible effect continues in the offspring after GC are discontinued, or whether the effects of GC can be modified if the dams are given GLP-2. Accord- ingly, this study was undertaken to determine (i) the influence of GLP-2, dexamethasone (DEX), and GLP-2 + DEX, when administered to pregnant and lactating rat dams, on the intesti- nal in vitro uptake of FA and cholesterol in their suckling off- spring; (ii) whether alterations in the uptake of lipids are due to variations in the intestinal morphology or mass, or to changes in selected lipid-binding proteins in the cytosol of the entero- cytes; and (iii) whether these changes persist a month later in postweaning animals. MATERIALS AND METHODS Animals. The principles for the care and use of laboratory ani- mals observed in the conduct of this study were approved by the Canadian Council on Animal Care and by the Council of the American Physiological Society. All experiments were ap- proved by the Animal Ethics Board, University of Alberta. Eight 1-wk-old pregnant Sprague Dawley rats were obtained from Bio Science Animal Services, University of Alberta. The dams were randomized into four groups and received treatment with GLP-2, DEX, GLP-2 + DEX, or a placebo. Treatment was started 10 d before delivery and was continued until the ani- mals were 19–21 d of age. DEX was administered in a dose of 0.128 μg/g body weight/d subcutaneously (sc) once per day at 7:00 PM. GLP-2 was administered in a dose of 0.1 μg/g body weight/d sc twice per day at 7:00 AM and 7:00 PM. The regi- men used for the DEX + GLP-2 group was DEX 0.128 μg/g Copyright © 2005 by AOCS Press 1141 Lipids, Vol. 40, no. 11 (2005) *To whom correspondence should be addressed at Division of Gastroenterol- ogy, Zeidler Ledcor Center, 130 University Campus, Edmonton, AB, Canada T6G 2X8. E-mail: alan.thomson@ualberta.ca Abbreviations: BBM, brush border membrane; DEX, dexamethasone; GC, glucocorticosteroid; GLP-2, glucagon-like peptide-2; GLP-2R, GLP-2 re- ceptor; I-FABP, intestinal fatty acid-binding protein; LCFA, long-chain fatty acids; L-FABP, liver fatty acid-binding protein; sc, subcutaneous; UWL, un- stirred water layer. Lipid Malabsorption Persists After Weaning in Rats Whose Dams Were Given GLP-2 and Dexamethasone Claudiu Iordache a , Laurie A. Drozdowski a , M. Tom Clandinin a , Gary Wild b , Zoe Todd a , and Alan B.R. Thomson a, * a Nutrition and Metabolism Group, Department of Medicine, University of Alberta, Edmonton, Alberta, Canada, and b Department of Anatomy and Cell Biology, McGill University, Montreal, Québec, Canada