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Long term hypoxia during gestation alters perirenal adipose tissue gene expression in the lamb.

ABSTRACT: We previously reported that following long-term hypoxia (LTH), the ovine foetus exhibits enhanced expression of brown/beige adipose genes. This study was designed to determine if these changes are preserved after birth. Pregnant ewes were divided among three groups, 1) Control, sea level, 2) LTH, high altitude (3,820 m, LTH-HA) from ~ day 40 of gestation through ~14 days post-delivery and 3) LTH from ⁓ day 40 through day 137 of gestation then returned to the laboratory where atory reduced maternal PO₂ was maintained by nitrogen infusion. Following delivery, lambs remained at sea level (LTH-SL). Perirenal adipose tissue was collected at ~day 14, and qRT-PCR was used to quantify mRNA. Uncoupling protein 1 (UCP-1), PPAR gamma coactivator 1 (PGC1α), and deiodinase-2 (DIO2) mRNA levels were significantly lower in both LTH groups while PR domain containing 16 (PRDM16) levels did not differ. Peroxisome proliferator-activated receptor (PPARγ) was maintained in the LTH-HA group and significantly increased in the LTH-SL group, compared to control. Unlike our previous LTH foetal studies, the brown/beige fat phenotype was rapidly lost by day 14 postpartum compared to control, while PPARγ was maintained. This loss of the brown fat phenotype may promote obesity due to decreased energy expenditure, favouring fat deposition.

SUBMITTER: Myers DA

PROVIDER: S-EPMC7238872 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:We hypothesized that maternal low or high nutrition would give unique effects to morphological and molecular dynamics in adipose tissue of fetus of fatty breed Wagyu (Japanese Black) cattle which produce highly marbled beef. This study aimed to determine the effects of maternal energy intake in Wagyu cows, during gestation on fetal adipose tissue development, histochemical properties, and gene and microRNA (miRNA) expression. Cows were allocated to one of two nutritional energy groups: 120% (HIGH) or 60% nutritional requirements of (LOW). Fetuses (n = 6 per treatment) were removed from pregnant cows by cesarean section at fetal age 260 ± 8 days and euthanized. Subcutaneous adipose tissue (SAT), thoracic cavity visceral adipose tissue (TVAT), and perirenal adipose tissue (PAT) were collected for analysis. In histochemical analysis, in SAT and PAT, HIGH fetuses had greater diameter of adipocytes than LOW fetuses (P<0.05). Only in SAT, LOW fetuses had more Leptin (LEP) mRNA and tended to have more Peroxisome Proliferator-Activated Receptor gamma (PPARG) CCAAT-enhancer-binding proteins alpha (CEBPA) and Glucose transporter (GLUT) 4 mRNA(P<0.10). In all SAT, TVAT, and PAT, LOW fetuses had higher levels of the brown adipose tissue (BAT) biomarkers Uncoupling Protein (UCP) 1 and PPARG coactivator (PGC) 1α mRNA than HIGH fetuses (P<0.08). Meanwhile, in the other adipose tissue, LOW fetuses had lower PPARG, CEBPA, and Zinc Finger Protein (ZFP) 423 (in TVAT and PAT), FASN (in TVAT), LEP and GLUT4 mRNA (in PAT; P<0.10). In particular, in TVAT and PAT, LOW fetuses exhibited lower expression of WAT biomarkers (PPARG and ZFP423). Differential expression of various miRNAs related to adipogenesis between the LOW and HIGH fetuses was detected in an adipose tissue-specific manner (P<0.10). Based on adipose tissue-specific effects of maternal nutrition, these findings suggested that poor maternal nutrition in Wagyu cattle increased BAT development in SAT, TVAT and PAT, while elevated maternal nutrition stimulated fetal SAT development compared with that of TVAT and PAT.

Project description:BackgroundRabbit is a good model for genetic and medical studies in other livestock species. The rabbit shows low adipose tissue deposition, and the phenomena indicates that there is some specificity of adipose deposition during the rabbit growth. However, little is known about genes that regulate the growth of adipose tissue in rabbits.Materials and methodsDeep RNA-seq and comprehensive bioinformatics analyses were used to characterize the genes of rabbit visceral adipose tissue (VAT) at 35, 85 and 120 days after birth. Differentially expressed genes (DEGs) were identified at the three growth stages by DESeq. To explore the function of the candidate genes, Gene Ontology (GO) enrichment and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses were performed. Six DEGs were randomly selected, and their expression profiles were validated by q-PCR.ResultsA total of 20,303 known transcripts and 99,199 new transcripts from 8 RNA sequencing libraries were identified, and 34 differentially expressed genes (DEGs) were screened. GO enrichment and KEGG pathway analyses revealed that the DEGs were mainly involved in lipid metabolism regulation including acylglycerol metabolic process and mobilization, and decomposition of lipids to generate ATP in adipocytes and fatty acid metabolism, included LOC100342322 and LOC100342572. In addition, 133 protein-coding genes that play a role in adipose growth and development were screened, including acyl-CoA synthetase long-chain family member 5 (ACSL5) and fatty acid-binding protein 2 (FABP2). The validation results of six DEGs by q-PCR showed similar trends with the results of RNA-seq.ConclusionIn summary, this study provides the first report of the coding genes profiles of rabbit adipose tissue during different growth stages. These data allow for the identification of candidate genes for subsequent studies on rabbit genetics and regulation of adipose cells, and provide an animal model for studying obesity in humans.

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Long term hypoxia during gestation alters perirenal adipose tissue gene expression in the lamb.

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