ESPE Abstracts (2016) 86 FC10.6

Developmental Programming of Somatic Growth, Behavior and the Endocannabinoid System (ECS) by Variation of Early Postnatal Nutrition in a Cross-Fostering Mouse Model

Felix Schreinera, Merle Ackermanna, Michael Michalika, Eva Rotherb, Andras Bilkei-Gorzoc, Ildiko Raczc, Jörg Dötschb, Andreas Zimmerc & Joachim Woelflea

aPediatric Endocrinology, Children’s Hospital, University of Bonn, Bonn, Germany; bPediatric Endocrinology, Children’s Hospital, University of Cologne, Cologne, Germany; cMolecular Psychiatry, University Hospital Bonn, Bonn, Germany

Background: Nutrient deprivation during early development has been associated with the predisposition to metabolic disorders in numerous epidemiological studies. Experiments with rodents also indicate a developmental plasticity of neuropsychological characteristics following alterations of early postnatal nutrition.

Objective: Considering its interaction with metabolism and regulation of appetite and behavior, the endocannabinoid system (ECS) may represent a promising target of early developmental programming.

Method: By using a cross-fostering strategy with variation of the litter size, early postnatal nutrition of CB6F1-hybrid mice was controlled during the lactation period (3, 6, or 10 animals per mother). After weaning, all pups received standard chow ad libitum. mRNA expression analyses (fat, liver, hypothalamus) were performed at age 50 days. In addition, we investigated locomotor activity and social behavior in standardized settings.

Results: Body growth was permanently altered, with differences for length, weight, BMI and visceral fat mass persisting beyond age 100 days according to early postnatal nutrition. This was paralleled by differences of hepatic IGF-I expression (3>6>10, P<0.01). Furthermore, distinct expression patterns for ECS key enzymes were observed in fat and liver. EC-synthetizing enzymes in adipose tissue tended to be higher expressed in formerly overfed mice (DAGLα P<0.05; NAPE-PLD P=0.05). Concordant expression patterns (3>6>10) were observed for EC-degrading enzymes FAAH (P<0.05, liver) and MGL (P<0.05, fat; P<0.01, liver). In the arcuate nucleus, formerly underfed mice tended to express more EC-receptor transcripts (CB1R P<0.05; CB2R P=0.08) than overfed animals. Open-field social behavior testing revealed significant differences, with formerly underfed mice turning out to be the most sociable animals (10>6>3, P<0.01). Locomotor activity was not different.

Conclusion: Our data indicate a developmental plasticity of growth, behavior and the ECS, with measurable impact of early postnatal over- and undernutrition. Developmental programming of the ECS in metabolically active tissues may play a role in the formation of the adult cardiometabolic risk profile following perinatal malnutrition in humans.