Unknown,Transcriptomics,Genomics,Proteomics

Dataset Information

ScRNA-seq of stromal vascular cells from 48 week (aged) mouse subcutaneous adipose tissue compared to control 10 week (young) mouse SVF

ABSTRACT: Adipose tissue mass and adiposity change throughout the lifespan. During aging, while visceral adipose tissue (VAT) tends to increase, peripheral subcutaneous adipose tissue (SAT) decreases significantly. Unlike VAT, which is linked to metabolic diseases, SAT has beneficial effects. However, the molecular details behind aging-associated loss of SAT remain unclear. Here we compare scRNA-seq of total SVF of SAT from young and aging mice to identify a novel Aging-dependent Regulatory Cell (ARC) that emerges in SAT of aged mice. Inguinal white adipose tissue (iWAT) was used as a representative SAT; iWAT pads of 2 mice from each age group were subjected to collagenase digestion and treated with a hypotonic buffer to remove red blood cells before subjection to scRNA-seq by 10X Genomics Chromium Single Cell Kit. The findings showed that ARCs express adipogenic markers but lack adipogenic capacity and inhibit differentiation of neighboring adipose precursors.

INSTRUMENT(S): 10X Genomics Chromium Single Cell Kit, Illumina NovaSeq 6000

ORGANISM(S): Mus musculus

SUBMITTER: Frances Lin

PROVIDER: E-MTAB-10221 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Publications

Aging-dependent regulatory cells emerge in subcutaneous fat to inhibit adipogenesis.

Nguyen Hai P HP Lin Frances F Yi Danielle D Xie Ying Y Dinh Jennie J Xue Pengya P Sul Hei Sook HS

Developmental cell 20210419 10

Adipose tissue mass and adiposity change throughout the lifespan. During aging, while visceral adipose tissue (VAT) tends to increase, peripheral subcutaneous adipose tissue (SAT) decreases significantly. Unlike VAT, which is linked to metabolic diseases, including type 2 diabetes, SAT has beneficial effects. However, the molecular details behind the aging-associated loss of SAT remain unclear. Here, by comparing scRNA-seq of total stromal vascular cells of SAT from young and aging mice, we iden ...[more]

PMID: 33878347

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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

ScRNA-seq of stromal vascular cells from 48 week (aged) mouse subcutaneous adipose tissue compared to control 10 week (young) mouse SVF

Publications

Aging-dependent regulatory cells emerge in subcutaneous fat to inhibit adipogenesis.

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