Universität zu Köln

Schreiner, Felix, Ackermann, Merle, Michalik, Michael, Hucklenbruch-Rother, Eva, Bilkei-Gorzo, Andras, Racz, Ildiko, Bindila, Laura, Lutz, Beat, Doetsch, Joerg, Zimmer, Andreas and Woelfle, Joachim (2017). Developmental programming of somatic growth, behavior and endocannabinoid metabolism by variation of early postnatal nutrition in a cross-fostering mouse model. PLoS One, 12 (8). SAN FRANCISCO: PUBLIC LIBRARY SCIENCE. ISSN 1932-6203

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Abstract

Background Nutrient deprivation during early development has been associated with the predisposition to metabolic disorders in adulthood. Considering its interaction with metabolism, appetite and behavior, the endocannabinoid (eCB) system represents a promising target of developmental programming. Methods By cross-fostering and variation of litter size, early postnatal nutrition of CB6F1-hybrid mice was controlled during the lactation period (3, 6, or 10 pups/mother). After weaning and redistribution at P21, all pups received standard chow ad libitum. Gene expression analyses (liver, visceral fat, hypothalamus) were performed at P50, eCB concentrations were determined in liver and visceral fat. Locomotor activity and social behavior were analyzed by means of computer-assisted videotracking. Results Body growth was permanently altered, with differences for length, weight, body mass index and fat mass persisting beyond P100 (all 3>6>10, p<0.01). This was paralleled by differences in hepatic IGF-I expression (p<0.01). Distinct gene expression patterns for key enzymes of the eCB system were observed in fat (eCB-synthesis: 3>6>10 (DAGL alpha p<0.05; NAPE-PLD p = 0.05)) and liver (eCB-degradation: 3>6>10 (FAAH p<0.05; MGL p<0.01)). Concentrations of endocannabinoids AEA and 2-AG in liver and visceral fat were largely comparable, except for a borderline significance for higher AEA (liver, p = 0.049) in formerly overfed mice and, vice versa, tendencies (p<0.1) towards lower AEA (fat) and 2-AG (liver) in formerly underfed animals. In the arcuate nucleus, formerly underfed mice tended to express more eCB-receptor transcripts (CB1R p<0.05; CB2R p = 0.08) than their overfed fellows. Open-field social behavior testing revealed significant group differences, with formerly underfed mice turning out to be the most sociable animals (p<0.01). Locomotor activity did not differ. Conclusion Our data indicate a developmental plasticity of somatic growth, behavior and parameters of the eCB system, with long-lasting impact of early postnatal nutrition. Developmental programming of the eCB system in metabolically active tissues, as shown here for liver and fat, may play a role in the formation of the adult cardiometabolic risk profile following perinatal malnutrition in humans.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Schreiner, Felix UNSPECIFIED UNSPECIFIED UNSPECIFIED Ackermann, Merle UNSPECIFIED UNSPECIFIED UNSPECIFIED Michalik, Michael UNSPECIFIED UNSPECIFIED UNSPECIFIED Hucklenbruch-Rother, Eva UNSPECIFIED UNSPECIFIED UNSPECIFIED Bilkei-Gorzo, Andras UNSPECIFIED UNSPECIFIED UNSPECIFIED Racz, Ildiko UNSPECIFIED UNSPECIFIED UNSPECIFIED Bindila, Laura UNSPECIFIED UNSPECIFIED UNSPECIFIED Lutz, Beat UNSPECIFIED UNSPECIFIED UNSPECIFIED Doetsch, Joerg UNSPECIFIED UNSPECIFIED UNSPECIFIED Zimmer, Andreas UNSPECIFIED UNSPECIFIED UNSPECIFIED Woelfle, Joachim UNSPECIFIED UNSPECIFIED UNSPECIFIED
URN:	urn:nbn:de:hbz:38-221331
DOI:	10.1371/journal.pone.0182754
Journal or Publication Title:	PLoS One
Volume:	12
Number:	8
Date:	2017
Publisher:	PUBLIC LIBRARY SCIENCE
Place of Publication:	SAN FRANCISCO
ISSN:	1932-6203
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language FOR-GESTATIONAL-AGE; CATCH-UP GROWTH; TUMOR-NECROSIS-FACTOR; ADIPOSE-TISSUE; INSULIN-RESISTANCE; CB1 RECEPTOR; CARDIOVASCULAR-DISEASE; LIPID-METABOLISM; GENE-EXPRESSION; SOCIAL-BEHAVIOR Multiple languages Multidisciplinary Sciences Multiple languages
Refereed:	Yes
URI:	http://kups.ub.uni-koeln.de/id/eprint/22133