Single cell functional genomics reveals plasticity of subcutaneous white adipose tissue (WAT) during early postnatal development
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ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE180589 | GEO | 2021/09/08
REPOSITORIES: GEO
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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.
2020-04-09 | PXD017306 | Pride
Project description:In our study, for identify the Myod-lineage precursor cells from inguinal WAT, the Myod-Cre; mTmG reporter mice were used. GFP+ (Myod-lineage) SVF progenitor cells from inguinal WAT (pooled from 3 animals) were sorted by FACS sorting, and plate in cell culture for total RNA isolation; as comparison, the Tomato+ SVF progenitor cells from the same tissue (pooled from 3 animals) were sorted by FACS sorting for total RNA isolation.
2018-08-15 | E-MTAB-6441 | biostudies-arrayexpress
Project description: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.
2014-04-04 | E-GEOD-56248 | biostudies-arrayexpress
Project description:We previously derived a doxycycline-inducible (Tet-On) lineage-tracing model that allows for the indelible labeling of Pdgfrb-expressing perivascular cells in adipose tissue of adult mice (PdgfrbrtTA; TRE-Cre; Rosa26RmT/mG; herein, MuralChaser mice). Prior to exposing animals to doxycyline, all cells within the stromal-vascular fraction (SVF) of adult inguinal WAT (iWAT) express membrane tdTomato from the Rosa26 locus. Following 9 days of exposure to doxycycline-containing chow diet, Cre-mediated excision of the loxP-flanked tdTomato cassette occurs in Pdgfrb-expressing cells, and membrane-bound GFP (mGFP) expression is constitutively activated. We set out to test the hypothesis that Pdgfrb-expressing perivascular cells in inguinal WAT of adult mice are heterogeneous, with subpopulations harboring functionally distinct phenotypes. To this end, we performed single cell RNA-sequencing of mGFP+ cells isolated from iWAT of lean (chow fed) 8 weeks-old male MuralChaser mice following 9 days of doxycycline exposure.
2020-09-01 | GSE144090 | GEO
Project description:Microarray analysis of white adipose tissue (WAT) and bone marrow adipose tissue (BMAT) from 22-week-old or 13-week-old male New Zealand White rabbits. From both cohorts, BMAT was sampled from the distal tibia (dBMAT) and the radius and ulna (ruBMAT), while WAT was sampled from the inguinal (iWAT) and gonadal (gWAT) depots. From the 13-week-old cohort, BMAT was also sampled from the proximal tibia (pBMAT). Sufficient RNA could not be isolated from all tissues for all rabbits, so for some rabbits only a subset of tissues is included.
2019-12-10 | GSE138690 | GEO
Project description:Inguinal white adipose tissue (iWAT) is essential for the beneficial effects of exercise training on metabolic health. The underlying mechanisms for these effects are not fully understood and here, we test the hypothesis that exercise training results in a more favorable iWAT structural phenotype. Using biochemical, imaging, and multi-omics analyses we find that 11-days of wheel running in male mice causes profound iWAT remodeling including decreased extracellular matrix (ECM) deposition, increased vascularization and innervation. We identify adipose stem cells as one of the main contributors to training-induced ECM remodeling, show that the PRDM16 transcriptional complex is necessary for iWAT remodeling and beiging, and discover neuronal growth regulator 1 (NEGR1) as a link between PRDM16 and neuritogenesis. Moreover, we find that training causes a shift from hypertrophic to insulin-sensitive adipocyte subpopulations. Exercise training leads to remarkable adaptations to iWAT structure and cell-type composition that can confer beneficial changes in tissue metabolism.
2023-10-24 | PXD040894 | Pride
Project description:Exosomes derived from adipose tissues (AT-Exos) have been identified as a crucialmedium in the transmission of information from adipose tissue to itself and to other organs, including exosomes derived from inguinal white adipose tissue (iWAT-Exos), visceral white adipose tissue (vWAT-Exos) and brown adipose tissue (BAT-Exos). However, the functional differences in depot-specific AT-Exos under obese conditions remain elusive. Here we reported that AT-Exos participated in regulating adipocyte inflammation and metabolic homeostasis. Notably, vWAT-Exos play a critical role in promoting lipid accumulation and inflammation in the development of obesity. Although both are derived from “energy storage” WAT, the biological effects exhibited by iWAT-Exos are far different from those vWAT-Exos. Especially under diet-induced obesity conditions, iWAT-Exos appeared to be BAT-Exo-like, exhibiting an “energy expending” type. Altogether, our data indicated that AT-Exos from different depots have distinct functions and effects on adipocytes metabolism.
2024-04-25 | GSE264480 | GEO
Project description:We investigated RNAs from Myod-lineage (GFP tagged) adipose tissue micro-dissected from inguinal WAT of Myod CRE; mTmG reporter mice (N=3). As comparison group, GFP- adipose tissue was dissected from inguinal WAT of the same mice (N=3) under microscope.
2018-08-15 | E-MTAB-6392 | biostudies-arrayexpress
Project description:Background: Excessive white adipose tissue (WAT) expansion as in obesity is generally associated with chronic inflammation of WAT, which contributes to obesity associated complications. Low oxygen availability in WAT is hypothesized to be the initiator of this inflammatory response. Hypothesis: We examined the hypothesis that local tissue hypoxia is responsible for the initiation of inflammation in WAT. Research design and methods: Diet-induced obese male C57BL/6JOlaHsd mice, housed at thermoneutrality, were exposed to mild environmental oxygen restriction (OxR, to 13% oxygen) for five days and compared with mice kept at normoxia, after which WAT and serum were collected. Body composition, systemic metabolic parameters, WAT macrophage infiltration (as marker for tissue inflammation) and whole genome microarray analysis, and circulating adipokines were measured. Results: Five days OxR decreased body weight and fat mass, and increased blood levels of haemoglobin and haematocrit, as well as lactate to glucose ratio, which indicated systemic hypoxia. No difference in adipose tissue inflammation was found, which was supported by down regulation of inflammation-associated transcript levels of S100a8, Saa1, and Saa3. Serum metabolomics revealed an increase of branched chain amino acid Valine and propionylcarnitine. Adipokines CCDC3, CCK, and Adiponectin are reduced by OxR on transcript (Cck) or serum protein level (Adiponectin), or both (CCDC3). Conclusions: Mild oxygen restriction does not increase white adipose tissue inflammation in obese mice. However, a systemic adaptation together with a metabolic response in WAT was observed.
2019-06-24 | GSE53802 | GEO