Metabolomics,Unknown,Transcriptomics,Genomics,Proteomics

Dataset Information

A Smooth Muscle-Like Origin for Beige Adipocytes

ABSTRACT: A comparison of the translating RNAs in UCP1-positive cells from the classical BAT, the inguinal WAT, and the perigonadal WAT. We find genes common to all UCP1-positive cells independent of anatomical location, as well as genes specifically enriched in one group versus the others. Results provide a portrait of gene expression in UCP1-positive cells in vivo. Translating RNAs in UCP1-positive cells were purified from 6 week old female UCP1-TRAP mice after 2 weeks at 4 degC. N=3 for iWAT, N=2 for pgWAT, and N=3 for BAT.

ORGANISM(S): Mus musculus

SUBMITTER: Jonathan Long

PROVIDER: E-GEOD-56248 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Publications

A smooth muscle-like origin for beige adipocytes.

Long Jonathan Z JZ Svensson Katrin J KJ Tsai Linus L Zeng Xing X Roh Hyun C HC Kong Xingxing X Rao Rajesh R RR Lou Jesse J Lokurkar Isha I Baur Wendy W Castellot John J JJ Rosen Evan D ED Spiegelman Bruce M BM

Cell metabolism 20140404 5

Thermogenic UCP1-positive cells, which include brown and beige adipocytes, transform chemical energy into heat and increase whole-body energy expenditure. Using a ribosomal profiling approach, we present a comprehensive molecular description of brown and beige gene expression from multiple fat depots in vivo. This UCP1-TRAP data set demonstrates striking similarities and important differences between these cell types, including a smooth muscle-like signature expressed by beige, but not classical ...[more]

PMID: 24709624

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Project description:Rodents are commonly housed below thermoneutrality (~20°C) 1. Under these conditions there is a substantial effect on rodent physiology including the hyperactivation of brown (BAT) and beige adipose tissue 2. Here, we raised animals from weaning, on an obesogenic diet at thermoneutrality (28°C) to closer mimic human physiology and determine the impact of a) moderate cold exposure (i.e. 20°C, a temperature reduction of ~8°C) or b) treatment with YM-178, a highly-selective, clinically used β3-adrenoreceptor agonist on classical BAT or subcutaneous inguinal (IWAT) beige depots. Under these conditions, uncoupling protein 1 mRNA was undetectable in IWAT in all groups. Maintenance at 20°C drove weight gain and a 125% increase in subcutaneous fat, an effect not seen with YM-178 administration thus suggesting a direct effect of ambient temperature in promoting weight gain and adiposity in obese rats. Using exploratory adipose tissue proteomics we reveal novel processes and pathways associated with cold-induced weight gain in BAT (i.e. histone deacetylation and glycosphingolipid biosynthesis) and IWAT (i.e. NAD+ binding and retinol metabolism). Conversely, YM-178 had minimal metabolic-related effects on BAT and drove a pro-inflammatory phenotype in IWAT. Exercise training elicits diverse effects on brown (BAT) and white adipose tissue (WAT) physiology in rodents housed below their thermoneutral zone (i.e. 28-32°C). In these conditions, BAT is chronically hyperactive and, unlike human residence, closer to thermoneutrality. Therefore, we set out to determine the effects of exercise training in obese animals at 28°C (i.e. thermoneutrality) on BAT and WAT in its basal (i.e. inactive) state. Sprague-Dawley rats (n=12) were housed at thermoneutrality from 3 weeks of age and fed a high-fat diet. At 12 weeks of age half these animals were randomised to 4-weeks of swim-training (1 hour/day, 5 days per week). Following a metabolic assessment interscapular and perivascular BAT and inguinal (I)WAT were taken for analysis of thermogenic genes and the proteome. Exercise attenuated weight gain but did not affect total fat mass or thermogenic gene expression. Proteomics revealed an impact of exercise training on2-oxoglutarate metabolic process, mitochondrial respiratory chain complex IV, carbon metabolism and oxidative phosphorylation. This was accompanied by an upregulation of multiple proteins involved in skeletal muscle physiology suggesting an adipocyte to myocyte switch in BAT. UCP1 mRNA was undetectable in IWAT with proteomics highlighting changes to DNA binding, the positive regulation of apoptosis, HIF-1 signalling and cytokine-cytokine receptor interaction.

Dataset Information

A Smooth Muscle-Like Origin for Beige Adipocytes

Publications

A smooth muscle-like origin for beige adipocytes.

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