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RNAseq analysis of brown adipose tissue (BAT) and thyroid of new-born lambs, subjected to short-term cold exposure, reveals signs of early whitening of BAT

ABSTRACT: RNAseq analysis of brown adipose tissue (BAT) and thyroid of new-born lambs, subjected to short-term cold exposure, reveals signs of early whitening of BAT

PROVIDER: PRJNA864845 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR20738039.fastq.gz	Fastqsanger.gz
	SRR20738040.fastq.gz	Fastqsanger.gz
	SRR20738041.fastq.gz	Fastqsanger.gz
	SRR20738042.fastq.gz	Fastqsanger.gz
	SRR20738043.fastq.gz	Fastqsanger.gz

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RNAseq analysis of brown adipose tissue (BAT) and thyroid of new-born lambs, subjected to short-term cold exposure, reveals signs of early whitening of BAT

Project description:An RNA-seq approach was utilized to characterise the transcriptome of brown adipose tissue and thyroid tissue in new-born Romney lambs after a short exposure (2 days) to cold conditions. This study provides an in-depth expression network of the main characters involved in thermogenesis and fat whitening mechanisms that take place in the new-born lamb.

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Extrauterine support of preterm lambs achieves similar transcriptomic profiling to late pre-term lamb brains

Project description:Our group has developed an extra-uterine environment for newborn development (EXTEND) using an ovine model, that aims to mimic the womb to improve short and long-term health outcomes associated with prematurity. This study’s objective was to determine the histologic and transcriptomic consequences of EXTEND on the brain. Histology and RNA-sequencing was conducted on brain tissue from three cohorts of lambs: control pre-term (106-107 days), control late pre-term (127 days), and experimental lambs who were born pre-term and supported on EXTEND until late pre-term age (125-128 days). Bioinformatic analysis determined differential gene expression among the three cohorts and across four different brain tissue sections: basal ganglia, cerebellum, hippocampus, and motor cortex. There were no clinically relevant histological differences between the control late pre-term and EXTEND ovine brain tissues. RNA-sequencing demonstrated that there was greater differential gene expression between the control pre-term lambs and EXTEND lambs than between the control late pre-term lambs and EXTEND lambs. Our study demonstrates that the use of EXTEND to support pre-term lambs until they reach late pre-term gestational age results in brain tissue gene expression that more closely resembles that of the lambs who reached late pre-term gestation within their maternal sheep’s womb than that of the lambs who were born prematurely.

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Project description:Brown adipose tissue (BAT) is a highly vascularized organ with abundant mitochondria that produce heat through uncoupled respiration. Obesity is associated with a reduction of BAT function; however, it is unknown how obesity promotes dysfunctional BAT. Here, using a murine model of diet-induced obesity, we determined that obesity causes capillary rarefaction and functional hypoxia in BAT, leading to a BAT “whitening” phenotype that is characterized by mitochondrial dysfunction, lipid droplet accumulation, and decreased expression of Vegfa. Targeted deletion of Vegfa in adipose tissue of nonobese mice resulted in BAT whitening, supporting a role for decreased vascularity in obesity-associated BAT. Conversely, introduction of VEGF-A specifically into BAT of obese mice restored vascularity, ameliorated brown adipocyte dysfunction, and improved insulin sensitivity. The capillary rarefaction in BAT that was brought about by obesity or Vegfa ablation diminished β-adrenergic signaling, increased mitochondrial ROS production, and promoted mitophagy. These data indicate that overnutrition leads to the development of a hypoxic state in BAT, causing it to whiten through mitochondrial dysfunction and loss. Furthermore, these results link obesity-associated BAT whitening to impaired systemic glucose metabolism.

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