title: Litter size reduction alters insulin signaling in the ventral tegmental area and influences dopamine-related behaviors in adult rats.
abstract: Postnatal overfeeding is a well-known model of early-life induced obesity and glucose intolerance in rats. However, little is known about its impact on insulin signaling in specific brain regions such as the mesocorticolimbic system, and its putative effects on dopamine-related hedonic food intake in adulthood. For this study, rat litters were standardized to 4 (small litter - SL) or 8 pups (control - NL) at postnatal day 1. Weaning was at day 21, and all tests were conducted after day 60 of life in male rats. In Experiment 1, we demonstrated that the SL animals were heavier than the NL at all time points and had decreased AKT/pAKT ratio in the Ventral Tegmental Area (VTA), without differences in the skeletal muscle insulin signaling in response to insulin injection. In Experiment 2, the standard rat chow intake was addressed using an automated system (BioDAQ, Research Diets(®)), and showed no differences between the groups. On the other hand, the SL animals ingested more sweet food in response to the 1 min tail-pinch challenge and did not develop conditioned place preference to sweet food. In Experiment 3 we showed that the SL rats had increased VTA TH content but had no difference in this protein in response to a sweet food challenge, as the NL had. The SL rats also showed decreased levels of dopamine D2 receptors in the nucleus accumbens. Here we showed that early postnatal overfeeding was linked to an altered functioning of the mesolimbic dopamine pathway, which was associated with altered insulin signaling in the VTA, suggesting increased sensitivity, and expression of important proteins of the dopaminergic system.
authors.affiliation: Departamento de Pediatria, Universidade Federal de Ciências da Saúde de Porto Alegre, Porto Alegre, Rio Grande do Sul, Brazil; Programa de Pós-Graduação em Saúde da Criança e do Adolescente, Departamento de Pediatria, Universidade Federal do Rio Grande do Sul, Brazil. Electronic address: akportella@gmail.com.
authors.forename: A K
authors.initials: AK
authors.lastname: Portella
authors.affiliation: Programa de Pós-Graduação em Saúde da Criança e do Adolescente, Departamento de Pediatria, Universidade Federal do Rio Grande do Sul, Brazil; Programa de Pós-Graduação em Neurociências, Instituto de Ciências Básicas da Saúde - Universidade Federal do Rio Grande do Sul, Porto Alegre, Rio Grande do Sul, Brazil.
authors.forename: P P
authors.initials: PP
authors.lastname: Silveira
authors.affiliation: Programa de Pós-Graduação em Neurociências, Instituto de Ciências Básicas da Saúde - Universidade Federal do Rio Grande do Sul, Porto Alegre, Rio Grande do Sul, Brazil.
authors.forename: D P
authors.initials: DP
authors.lastname: Laureano
authors.affiliation: Programa de Pós-Graduação em Saúde da Criança e do Adolescente, Departamento de Pediatria, Universidade Federal do Rio Grande do Sul, Brazil.
authors.forename: S
authors.initials: S
authors.lastname: Cardoso
authors.affiliation: Programa de Pós-Graduação em Saúde da Criança e do Adolescente, Departamento de Pediatria, Universidade Federal do Rio Grande do Sul, Brazil.
authors.forename: V
authors.initials: V
authors.lastname: Bittencourt
authors.affiliation: Programa de Pós-Graduação em Saúde da Criança e do Adolescente, Departamento de Pediatria, Universidade Federal do Rio Grande do Sul, Brazil.
authors.forename: C
authors.initials: C
authors.lastname: Noschang
authors.affiliation: Programa de Pós-Graduação em Saúde da Criança e do Adolescente, Departamento de Pediatria, Universidade Federal do Rio Grande do Sul, Brazil.
authors.forename: I
authors.initials: I
authors.lastname: Werlang
authors.affiliation: Programa de Pós-Graduação em Saúde da Criança e do Adolescente, Departamento de Pediatria, Universidade Federal do Rio Grande do Sul, Brazil.
authors.forename: F U
authors.initials: FU
authors.lastname: Fontella
authors.affiliation: Programa de Pós-Graduação em Neurociências, Instituto de Ciências Básicas da Saúde - Universidade Federal do Rio Grande do Sul, Porto Alegre, Rio Grande do Sul, Brazil.
authors.forename: C
authors.initials: C
authors.lastname: Dalmaz
authors.affiliation: Programa de Pós-Graduação em Saúde da Criança e do Adolescente, Departamento de Pediatria, Universidade Federal do Rio Grande do Sul, Brazil.
authors.forename: M Z
authors.initials: MZ
authors.lastname: Goldani
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D001835:Body Weight / Q000502:physiology; D003216:Conditioning, Operant / Q000502:physiology; D004298:Dopamine / Q000378:metabolism*; D004435:Eating / Q000502:physiology; D005518:Food Preferences / Q000502:physiology; D007328:Insulin / Q000378:metabolism*; D008098:Litter Size; D008297:Male; D018482:Muscle, Skeletal / Q000502:physiology; D009714:Nucleus Accumbens / Q000378:metabolism; D051058:Oncogene Protein v-akt / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D011954:Receptors, Dopamine / Q000378:metabolism; D015398:Signal Transduction / Q000502:physiology*; D013315:Stress, Psychological / Q000473:pathology / Q000503:physiopathology; D013997:Time Factors; D014446:Tyrosine 3-Monooxygenase / Q000378:metabolism; D017557:Ventral Tegmental Area / Q000378:metabolism*
chemical_list: D007328:Insulin; D011954:Receptors, Dopamine; D014446:Tyrosine 3-Monooxygenase; D051058:Oncogene Protein v-akt; D004298:Dopamine
keywords: Dopamine; Feeding behavior; Insulin; Postnatal overfeeding