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Effects on transcriptional regulation and lipid droplet characteristics in the liver of female juvenile pigs after early postnatal feed restriction and refeeding are dependent on birth weight

ABSTRACT: Low (U) and normal (N) birth weight female porcine offspring were used to study molecular and physiological changes in the liver before and after postnatal feed restriction (R, 50% of controls) and after subsequent refeeding period in comparison to non-restricted control animals (K). Overall, the following questions were addressed at the transcriptional, epigenomic and metabolic level: 1) Are there differences in the hepatic transcriptional profile between U and normal birth weight 2) Are these effects reflected on the metabolic level? 3) Could the possible birth weight-dependent effects be modified through feed restriction intervention? 4) Are these effects persistent and, moreover, can improvements with regard to lipid homeostasis be observed? Microarrays were used to study the effects of birth weight and/or feed restriction on the transcriptional level.

ORGANISM(S): Sus scrofa

PROVIDER: GSE43826 | GEO | 2016/01/23

SECONDARY ACCESSION(S): PRJNA187507

REPOSITORIES: GEO

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Project description:Moderate caloric restriction (CR) and weight loss are beneficial for the promotion of health; however, there is controversy regarding the effects of dieting regimens on behavior. In this study, we investigated two different dieting regimens: repeated fasting and refeeding (RFR) and daily feeding of half the amount of food consumed by RFR mice (CR). Mice in both regimens were subjected to 20% reduction in food intake and transiently reduced their body weights during the first 12 days of the study. Open field, light-dark transition, elevated plus maze, and forced swimming tests indicated that CR, but not RFR, reduced anxiety- and depressive-like behaviors, with a peak on day 8. Using a mouse whole genome microarray, we analyzed gene expression in the prefrontal cortex, amygdala, and hypothalamus. In addition to the caloric restriction-responsive genes commonly modified by RFR and CR, each regimen differentially changed the expression of distinct genes in each region. The most profound change was observed in the amygdala of CR mice: 884 genes were specifically up-regulated. Ingenuity pathway analysis showed that these 884 genes significantly modified 9 canonical pathways in the amygdala. alpha-adrenergic and dopamine receptor signaling were the two top-scoring pathways. Quantitative real-time RT-PCR confirmed the up-regulation of 6 genes in these pathways. Ppp1r1b encoded Darpp-32 including dopamine receptor signaling, and the increased protein was specific for CR mice. Our results suggest that moderate CR may modify anxiety- and depressive-like behaviors and alter gene expression especially in the mouse amygdala. Experiment Overall Design: We tested three feeding regimens. One group of mice had ad libitum (AD) access to food, and was used as a control group. The repeated fasting and refeeding (RFR) group of mice were fasted on day 0 and allowed to feed ad libitum on day 1. Amounts of food consumed by the three mice on day 1 were measured. The half amount of food consumed by the RFR mice was given to three mice in another cage for two days (days 0 and 1) (CR group). The fasting followed by refeeding (RFR) and the restriction of food (CR) were repeated up to day 16. Body weights and consumed chow were measured at 20:00 every day, and then the fasting or feeding period was started. In RFR mice, fasting was started on day 0.Total RNA was prepared from the prefrontal cortex, hypothalamus, and amygdala in the mice of each group on day 8. An equal amount of RNA from 4 mice in each group was pooled and used for microarray analysis.

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Effects on transcriptional regulation and lipid droplet characteristics in the liver of female juvenile pigs after early postnatal feed restriction and refeeding are dependent on birth weight

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