Effect of neonatal β(3)-adrenoceptor agonist CL 316,243 treatment on body fat accumulation and intestinal alkaline phosphatase activity in rats from reduced nests.

Introduction: The aim of this study was to evaluate the effects of early life administration of β3-adrenoceptor agonist (CL 316,243) on somatic and feeding parameters, obesity development as well as small intestinal enzyme activity in 21- and 40-day-old overfed male Sprague-Dawley rats.

Material And Methods: To induce postnatal overnutrition, litter size was reduced to 4 pups/litter (small litters, SL); while in normally-nourished groups (NL) the litter size was adjusted to 10 pups/litter. From days 5 to 15, half of the suckling pups from NL and SL groups received CL 316,243 subcutaneously. From 21st to 40th day, in the post-weaning period, both control (NL, SL) and CL 316,243-treated (NL-CL, SL-CL) rats had free access to standard diet and water. Body composition was determined by magnetic resonance imaging, blood pressure was measured using non-invasive tail-cuff, and intestinal alkaline phosphatase (AP) activity was assessed by histochemistry.

Results: At 21 and 40 days of age the SL rats showed higher body mass, displayed higher adiposity and had significantly increased duodenal and jejunal AP activity compared with NL animals. On day 21, NL and SL rats treated with CL 316,243 showed significantly less fat deposition and jejunal AP activity than the non-treated controls. In contrast, treatment-related changes in adiposity and AP activity were not observed in 40-day-old NL-CL, SL-CL rats.

Conclusions: These results indicate that early pharmacological intervention with CL did not permanently influence physiological processes involved in body weight/fat regulation, which resulted in the development of early-programmed overweight status in SL rats after weaning.