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The transcriptional basis of a developmental transition from brown to white adipose tissue.

ABSTRACT: Next Generation Sequencing (NGS) was used to measure the levels of gene transcription in perirenal adipose tissue (PRAT) in late gestation sheep fetuses (~ 2 weeks before birth) and in 12 week old lambs.

ORGANISM(S): Ovis aries

PROVIDER: GSE69953 | GEO | 2019/07/01

REPOSITORIES: GEO

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Project description:Expression data from Sheep longissimus dorsi (LD) muscle during development; fetal lambs (80, 100, 120 days gestation), new born lambs at birth (150 d) and lambs at 12 weeks (230 d) The fetal to neonatal developmental transition corresponds with profound changes in skeletal muscle function as it adapts to the new physiological demands of locomotion and postural support against gravity. The mechanisms underpinning this adaption process are unclear but are likely to be initiated by changes in hormone levels occurring during the major developmental transition. We tested the hypothesis that this period is associated with changes in the transcription of skeletal muscle genes, particularly genes involved in oxidative metabolism. Using an ovine model, transcriptional profiling was performed on longissimus dorsi skeletal muscle taken at three fetal developmental time points (80, 100 and 120 d of fetal development) as well as two postnatal time points, one within 3 days after birth and a second at 12 weeks of age. The developmental time course was dominated by large changes in the expression of 2471 genes during the period from late fetal development (120 d fetal development) to birth (within 1-3 days of birth). Analysis of the functions of the genes that were uniquely up-regulated in this period showed strong enrichment for oxidative metabolism and the TCA cycle indicating enhanced mitochondrial activity. Indeed, histological examination of tissues from these developmental time points directly demonstrated a marked increase in mitochondrial activity between the late fetal and early post-natal samples. The genes that were down-regulated in this period suggested de-emphasis of an array of biological functions including Wnt signaling, cell adhesion and differentiation. There were also changes in the expression of genes prior to this late fetal â postnatal transition and between the two postnatal time points that involved a variety of biological functions. It is concluded that there is substantial and coordinated changes in the transcription of a large number of genes in skeletal muscle which underpin the adaption of muscle to the new physiological demands in the postnatal environment. Microarrays were used for transcription profiling of skeletal muscle samples taken from fetal lambs (80, 100, 120 days gestation), new born lambs at birth (150 d) and lambs at 12 weeks (230 d) Sheep used in this experiment were bred from a research flock of Dorset/Suffolk/Rambouillet cross-bred sheep raised at Utah State University and cared for and euthanased for sample collection in accordance with the animal ethics guidelines of Utah State University (Utah, USA). Longissimus dorsi (LD) skeletal muscle samples were taken from fetal lambs at 80, 100 and 120 days of gestation, new born lambs within 1 to 3 days of birth (i.e. 150 days of development) and young lambs at 12 weeks of age (230 days of development). Three individuals were sampled at each developmental time

Project description:Worldwide, fetal growth restriction (FGR) affects 7 to 10% of pregnancies, or roughly 20.5 million infants, each year. FGR not only increases neonatal mortality and morbidity but also the risk of obesity in later life. Currently, the molecular mechanisms by which FGR "programs" an obese phenotype are not well understood. Studies demonstrate that FGR females are more prone to obesity compared to males; however, the molecular mechanisms that lead to the sexually dimorphic programming of FGR are not known. Thus, we hypothesized that FGR leads to the sexually dimorphic programming of preadipocytes and reduces their ability to differentiate into mature adipocytes. To test the hypothesis, we utilized a maternal hyperthermia-induced placental insufficiency to restrict fetal growth in sheep. We collected perirenal adipose tissue from male and female near-term FGR and normal-weight fetal lambs (N=4 in each group, 16 total), examined the preadipocytes' differentiation potential, and identified differential mRNA transcript expression in perirenal adipose tissue. Male FGR fetuses have lower cellular density compared to control male fetuses. However, no difference was observed in female FGR fetuses compared to control female fetuses. In addition, the ability of preadipocytes to differentiate into mature adipocytes with fat accumulation was impaired in male FGR fetuses, but this was not observed in female FGR fetuses. Finally, we examined the genes and pathways involved in the sexually dimorphic programming of obesity by FGR. On enrichment of differentially expressed genes in males compared to females, the Thermogenesis KEGG Pathway was downregulated, and the Metabolic and Steroid Biosynthesis KEGG pathways were upregulated. On enrichment of differentially expressed genes in male FGR compared to male control, the Steroid Biosynthesis KEGG Pathway was downregulated, and the PPAR Signaling KEGG pathway was upregulated. No pathways were altered in females in response to growth restriction in perirenal adipose tissue. Thus, the present study demonstrates a sexually dimorphic program in response to growth restriction in sheep fetal perirenal adipose tissue.