Transcriptomic analysis of brown adipose tissue across the physiological extremes of natural hibernation.

Marshall Hampton,Richard G Melvin,Matthew T Andrews,Karin Dahlman-Wright

doi:10.1371/journal.pone.0085157

Marshall Hampton, Richard G Melvin + Show 2 more

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https://doi.org/10.1371/journal.pone.0085157

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Journal: PloS one	Publication Date: Dec 30, 2013
Citations: 130	License type: CC BY 4.0

Affiliation: University of Minnesota, Duluth

Abstract

We used RNAseq to generate a comprehensive transcriptome of Brown Adipose Tissue (BAT) over the course of a year in the naturally hibernating thirteen-lined ground squirrel, Ictidomys tridecemlineatus. During hibernation ground squirrels do not feed and use fat stored in White Adipose Tissue (WAT) as their primary source of fuel. Stored lipid is consumed at high rates by BAT to generate heat at specific points during the hibernation season. The highest rate of BAT activity occurs during periodic arousals from hypothermic torpor bouts, referred to as Interbout Arousals (IBAs). IBAs are characterized by whole body re-warming (from 5 to 37 °C) in 2-3 hours, and provide a unique opportunity to determine the genes responsible for the highly efficient lipid oxidation and heat generation that drives the arousal process. Illumina HighSeq sequencing identified 14,573 distinct BAT mRNAs and quantified their levels at four points: active ground squirrels in April and October, and hibernating animals during both torpor and IBA. Based on significant changes in mRNA levels across the four collection points, 2,083 genes were shown to be differentially expressed. In addition to providing detail on the expression of nuclear genes encoding mitochondrial proteins, and genes involved in beta-adrenergic and lipolytic pathways, we identified differentially expressed genes encoding various transcription factors and other regulatory proteins which may play critical roles in high efficiency fat catabolism, non-shivering thermogenesis, and transitions into and out of the torpid state.

Highlights

Almost all mammals possess Brown Adipose Tissue (BAT) as infants to help maintain their body temperature through nonshivering thermogenesis
Total RNA was prepared from BAT during various activity states at four different times of the year: April active, October active, January torpid, and interbout arousal (Figure 1)
We identified 14,573 distinct transcripts in ground squirrel BAT that mapped to human mRNAs (Table S1)

Summary

Introduction

Almost all mammals possess Brown Adipose Tissue (BAT) as infants to help maintain their body temperature through nonshivering thermogenesis. Unlike White Adipose Tissue (WAT), which serves as the main fat storage depot in children and adults, BAT has evolved to generate heat in newborn and hibernating mammals (reviewed in [1]). Mammals that hibernate retain BAT as adults in order to efficiently re-warm themselves when arousing from hypothermic torpor. Stored lipid is consumed at high rates by BAT to generate heat at specific points during the hibernation season. The highest rate of BAT activity occurs during multiple arousals from hypothermic torpor bouts referred to as Interbout Arousals (IBAs). IBAs provide a unique opportunity to determine the molecular factors in BAT that are responsible for the highly efficient fat burning activity that drives the arousal process. During the 2-3 hour transition out of torpor, O2 consumption increases 50-fold, heart rate explodes from less than 10 beats per minute (bpm) to over 400 bpm, and body temperature increases from 5 to 37°C [9]

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