Adaptation of white adipose tissue to cool environmental temperatures
Ontology highlight
ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE169142 | GEO | 2021/04/28
REPOSITORIES: GEO
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Project description:Laboratory mice are standardly housed around 23ºC, setting them under chronic cold stress. Metabolic changes of liver in mice housed under thermoneutral, standard and cold temperatures remain unknown. Here we isolated lipid droplets and mitochondria from their livers for comparative proteomic study to investigate the changes. According to proteomic analysis, mitochondrial TCA cycle and retinol metabolism were enhanced while oxidative phosphorylation was no obviously affected under cold condition, suggesting liver mitochondria may increase TCA cycle capacity in biosynthetic pathways as well as retinol metabolism to help liver to adapt. Based on proteomic and immunoblotting results, Perilipin 5 and major urinary proteins were increased significantly while mitochondrial pyruvate carrier was decreased dramatically under cold condition, indicating a role they may play.
2019-07-02 | PXD014224 | Pride
Project description:Purpose: To identify the impact of thermoneutral housing as opposed to standard housing on gene expression profiles in the mouse peripheral blood mononuclear cells (PBMCs), focusing on proinflammatory immune responses and high-fat diet induced non-alcoholic fatty liver disease pathogenesis. Methods: Expression profiles from PBMCs collected from C57Bl6 mice fed chow or high-fat diet for 8 weeks, following 2 weeks at either standard or thermoneutral housing conditions. Sequencing was performed in duplicate, the Illumina HiSeq 2500. Transcripts that passed quality filters were analyzed at the gene level, using Strand NGS for accurate alignment and quantification. Results: We mapped approximately 20million reads per sample to the mm10 genome using annotations produced by Ensembl, which represented 36186 transcripts. Approximately 14000 genes exhibited reasonable expression in at least one experimental condition. The primary focus was the effect of housing temperature while holding diet consistent (i.e. thermoneutral vs standard, both on high-rat diet), where ~2700 genes exhibited differential regulation. Conclusions: We present the transcriptomic profile of PBMCs from mice fed chow of high-fat diets, following either standard or thermoneutral housing. We obseve an augmented proinflammatory immune response.
2017-02-12 | GSE80976 | GEO
Project description:Most studies using murine disease models are conducted at a housing temperature of 20ºC that is sub-optimal (ST) for mice, eliciting changes in metabolism and response to disease. Experiments performed at a thermoneutral temperature (TT) of 37ºC have revealed an altered immune response to pathogens and experimental treatments in disease models (e.g. cancer, obesity, Alzheimer’s disease). These alterations in metabolic activity have implications for the use of murine models to understand human diseases and their translation to clinical research. How such conditions affect the inflammatory response to infection with Plasmodium berghei ANKA (PbA) and subsequent disease progression is unknown. We hypothesized that changes in environmental temperature modulate immune cells and modify host response to malaria disease. To test this hypothesis, we conducted two sets of experiments to determine: (1) the inflammatory response of bone-marrow derived macrophages (BMDM) to infectious agents at different environmental temperatures and (2a) the inflammatory response to malarial agents injection in a peritonitis model and (2b) disease progression in PbA-infected mice at TT compared to ST. Firstly, BMDMs were incubated and stimulated with LPS at a fever-like temperature (FT; 39ºC), TT (37ºC) or low-temperatures (LT; 30ºC) mimicking ST for 6, 12 and 24 hours. We observed an that BMDMs released increased inflammation markers (i.e. nitric oxide and pro-inflammatory cytokine at FT and TT compared to LT, with an increase overtime. Secondly, C57BL6 mice were acclimatized for 3 weeks at TT (28 – 31ºC) or ST (20 – 22ºC). In one study, mice were injected intraperitoneally with nHZ or Leishmania at both temperatures, and immune cells were counted and subtyped from the peritoneal cavity (PEC) fluid. Cytokine concentrations and extracellular vesicle (EV) profiles were also determined from the PEC. Apart from Leishmania injection resulting in decreased cell recruitment and a higher phagocytosis of nHZ in mice housed at TT, we did not observe many temperature-based differences. We found 398 upregulated and 293 downregulated pro-inflammatory genes in mice injected with nHZ, that were similar to those previously elicite with Leishmania injections, at both temperatures. EV profile did not differ significantly at TT compared to ST but we report the presence of proteosome-derived and platelet-derived EVs in a murine parasitic murine model at both temperatures. In another study, mice were injected with luciferase-tagged PbA-infected RBCs and monitored until death. We observed metabolic changes (i.e. lower body weight and temperature loss) in mice housed at TT but these did not result to noticeable changes in survivability, parasite organ sequestration or serum cytokine levels compared to ST. To our knowledge, these experiments are the first to investigate the effect of thermoneutrality on a malaria murine model. Despite results suggesting that thermoneutrality does not significantly alter severe malarial disease progression or host inflammatory response to parasitic agents, we found important metabolic difference in mice housed at TT. Our results offer insights on how thermoneutrality might impact a severe malaria murine model and directions for more targeted investigations. This constitutes a first step in elucidating factors that may explain the lack of translatability to clinical trial.
2023-05-24 | GSE221454 | GEO
Project description:Environmental enrichment (EE) is a robust intervention for reducing cocaine-seeking behaviors in animals when given during abstinence. However, the mechanisms that underlie these effects have not been well-established. We investigated the adult male rat transcriptome using RNA-sequencing (RNA-seq) following differential housing during abstinence from cocaine self-administration for either 1 or 21 days. Rats housed for 21 days of abstinence in EE displayed a significant reduction in cocaine-seeking behavior compared to rats housed in isolation. RNA-seq of the nucleus accumbens shell revealed hundreds of differentially regulated transcripts between rats of different abstinence length and housing environment, as well as within specific contrasts such as enrichment (isolated 21 days vs. enriched 21 days) or incubation (isolated 1 day vs. isolated 21 days). Ingenuity Pathway Analysis affirmed several pathways as differentially enriched based on housing condition and abstinence length including RELN, the Eif2 signaling pathway, synaptogenesis and neurogenesis pathways. Additionally, multiple pathways reversed their directionality between enrichment and incubation contrasts, potentially indicating oppositional roles across housing and abstinence length. Together, these findings reveal novel mechanisms potentially involved in the protective effects of EE against cocaine seeking, which may inform efforts to develop new pharmacological and gene therapies for treating cocaine use disorders.
2020-07-15 | GSE144606 | GEO
Project description:Thermoneutral housing regulates intestinal tissue tolerance
| PRJNA665457 | ENA
Project description:Adaptation of white adipose tissue to cool environmental temperatures
| PRJNA715436 | ENA
Project description:Mice have their lowest (basal) metabolic rate when housed at thermoneutrality, which starts above 29 degrees C. Although they eat less, and thus reduce their energy intake, their energy balance remains positive leading to an increased adiposity, especially when fed a high fat diet. However, almost all metabolic mouse studies are performed at standard room temperatures ranging between 20 and 22 degrees C. Previously, we showed that housing mice at thermoneutrality lead to massive increased adiposity, while metabolic dysfunction of white adipose tissue (WAT) was absent. Here, we studied whether an increased metabolic flux through WAT induces cellular stress and underlies tissue dysfunction leading to tissue inflammation. C57BL/6JOlaHsd wildtype male mice, aged 9 weeks, were fed purified low fat diet (BIOCLAIMS, Hoevenaars et al., Genes and Nutrition 2012) for 3 weeks to acclimatize, followed by 12 weeks a BIOCLAIMS high-fat diet (HFD), all at thermoneutrality (29 degrees C). Subsequently, mice were divided into different treatment groups: i) control group, which remained at thermoneutrality for 5 days, ii) 5 days normal housing temperature (22 C degrees) while housed continously in an indirect calorimetry system. At the end of the study, after 2 hours food removal at the start of the light phase, mice were killed immediately by decapitation after taking them out of the indirect calorimetry system. After sacrification, epididymal WAT was immediately dissected and snap frozen in liquid nitrogen. Total RNA was isolated, quantified and qualified, and subsequently used for global gene expression profiling using Agilent 8x60K microarrays.
2017-04-06 | GSE53804 | GEO
Project description:The experiment mapped changes in RNA that occur as adipocytes adapt to cool temperatures (31°C ) in vitro. We performed RNA-Seq on mature adipocytes exposed to 31°C for 0, 1 or 12 days. 0 day refers to the control, where cells were cultured at 37°C only.
2021-04-28 | GSE159451 | GEO
Project description:Laboratory mice are standardly housed around 23ºC, setting them under chronic cold stress. Metabolic changes of liver in mice housed under thermoneutral, standard and cold temperatures remain unknown. Here we isolated lipid droplets and mitochondria from their livers for comparative proteomic study to investigate the changes. According to proteomic analysis, mitochondrial TCA cycle and retinol metabolism were enhanced while oxidative phosphorylation was no obviously affected under cold condition, suggesting liver mitochondria may increase TCA cycle capacity in biosynthetic pathways as well as retinol metabolism to help liver to adapt. Based on proteomic and immunoblotting results, Perilipin 5 and major urinary proteins were increased significantly while mitochondrial pyruvate carrier was decreased dramatically under cold condition, indicating a role they may play.
2019-07-17 | MSV000084105 | MassIVE
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