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. 2018 Jul 1;50(7):495-503.
doi: 10.1152/physiolgenomics.00002.2018. Epub 2018 Apr 6.

Adipose Transcriptome Analysis Provides Novel Insights Into Molecular Regulation of Prolonged Fasting in Northern Elephant Seal Pups

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Free PMC article

Adipose Transcriptome Analysis Provides Novel Insights Into Molecular Regulation of Prolonged Fasting in Northern Elephant Seal Pups

Bridget Martinez et al. Physiol Genomics. .
Free PMC article

Abstract

The physiological and cellular adaptations to extreme fasting in northern elephant seals ( Mirounga angustirostris, NES) are remarkable and may help to elucidate endocrine mechanisms that regulate lipid metabolism and energy homeostasis in mammals. Recent studies have highlighted the importance of thyroid hormones in the maintenance of a lipid-based metabolism during prolonged fasting in weaned NES pups. To identify additional molecular regulators of fasting, we used a transcriptomics approach to examine changes in global gene expression profiles before and after 6-8 wk of fasting in weaned NES pups. We produced a de novo assembly and identified 98 unique protein-coding genes that were differentially expressed between early and late fasting. Most of the downregulated genes were associated with lipid, carbohydrate, and protein metabolism. A number of downregulated genes were also associated with maintenance of the extracellular matrix, consistent with tissue remodeling during weight loss and the multifunctional nature of blubber tissue, which plays both metabolic and structural roles in marine mammals. Using this data set, we predict potential mechanisms by which NES pups sustain metabolism and regulate adipose stores throughout the fast, and provide a valuable resource for additional studies of extreme metabolic adaptations in mammals.

Keywords: adipose; de novo assembly; extracellular matrix; fasting; transcriptome.

Figures

Fig. 1.
Fig. 1.
Top 20 KEGG pathways significantly enriched in the fasting elephant seal pup blubber transcriptome relative to the human genome (P < 0.05, corrected for multiple hypothesis testing with the Benjamini-Hochberg method, DAVID v6.8). Bars show number of annotated seal genes mapping to each category.
Fig. 2.
Fig. 2.
Volcano plot of blubber gene expression changes during fasting in elephant seal pups. The x-axis shows log2 fold change, and the y-axis shows significance (–log10 adj. P value). Differentially expressed genes (log2 fold change ≥|1|, adj. P value < 0.05) are shown in yellow (upregulated) and violet (downregulated).
Fig. 3.
Fig. 3.
KEGG pathways (violet) and Gene Ontology (GO) Biological Process categories (yellow) overrepresented in the set of genes that were downregulated during fasting in blubber of elephant seal pups, relative to the human genome (adj. P < 0.05). −LogP, −log10(adj. P value); count, number of transcripts mapping to each process or pathway; ECM, extracellular matrix.
Fig. 4.
Fig. 4.
Summary diagram with differentially expressed genes grouped by their known function in metabolism in mammals. Upregulated genes are shown in yellow, downregulated genes are shown in violet.

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