Transcriptome profiling of mouse subcutaneous white adipose tissue treated with BML-260
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ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE129771 | GEO | 2019/04/14
REPOSITORIES: GEO
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Project description:To explore BML-260 how to increase thermogenesis, we treated brown adipocytes with BML-260 and DMSO for 1 day or 3 days after seven days' differenciation. Meanwhile, we also set ISO (isoproterenol)-treated brown adipocytes as positive control. We found that BML-260 treatment led to very significant upregulation of genes involved in oxidative phosphorylation, fatty acid beta-oxidation, and mitochondrial function.When compared to cells treated with ISO, although both showed significant upregulation of UCP1, BML-260-treated cells showed a rather distinct gene profile when compared to ISO-treated cells. This work provides evidences that BML-260 can also exert a JSP-1-independent effect in activating UCP1 and thermogenesis in adipocytes, and be potentially applied to treat obesity.
2019-04-16 | GSE129791 | GEO
Project description:Non-shivering thermogenesis in adipocytes is mediated by brown adipose tissue, purportedly through the sole action of uncoupling protein 1 (UCP1). The physiological relevance of UCP1-dependent thermogenesis has primarily been inferred from the attenuation of thermogenic output of mice genetically lacking Ucp1 from birth (germline Ucp1-/-). However, germline Ucp1-/- mice harbor secondary changes within brown adipose tissue beyond UCP1, such as reduced electron transport chain abundance. We show here that these secondary changes also encompass reduced expression of genes regulating fuel liberation, changes that would attenuate the capacity of any thermogenic pathway. Therefore, the quantitative contribution of UCP1-dependent and -independent thermogenesis is not fully understood. To mitigate the potentially confounding ancillary changes to brown adipose tissue of germline Ucp1-/- mice, we constructed mice with inducible adipocyte-selective disruption of Ucp1. We find that, while germline Ucp1-/- mice succumb to cold-induced hypothermia with complete penetrance, most mice with inducible deletion of Ucp1 maintain homeothermy in the cold. However, inducible adipocyte-selective co-deletion of Ucp1 and creatine kinase B (Ckb, an effector of UCP1-independent thermogenesis) exacerbates cold-intolerance, indicative of a negative genetic interaction and thus a parallel thermogenic function. We find no evidence for impairments in insulation or non-shivering thermogenesis in skeletal muscle that would drive this phenotype. Furthermore, following UCP1 deletion or UCP1/CKB co-deletion from mature adipocytes, moderate cold exposure triggers the regeneration of mature adipocytes that coordinately restore UCP1 and CKB to brown adipose tissue, providing further evidence of their parallel thermogenic relationship. Our findings suggest that thermogenic adipocytes utilize non-paralogous protein redundancy – through UCP1 and CKB – to promote cold-induced energy dissipation.
2024-01-10 | PXD047841 | Pride
Project description:*Background: Adipocytes mainly function as energy storage and endocrine cells. The amount and distribution of fat are important factor that influence the meat quality in the beef industry. Fat depot can be found around internal organ (ometal), beneath the skin (subcutaneous), and between muscles (intramuscular). Different adipose depot showed the biological and genetic difference depending on their location. This inter-depot variation might be influenced by the inherent genetic programing for development of adipose depots. In this study, we used RNA-seq data to investigate the difference in transcriptome of various adipose depots in Hanwoo. *Results: Using RNA-seq, we identified 5797, 2156, and 5455 DEGs in the comparison between OI, OS, and IS respectively (FDR<0.01) and found 853, 48, and 979 DEGs specific to subcutaneous, intramuscular and omental fat respectively. DEGs in intramuscular fat were highly enriched the metabolism related pathways compared to other fat depots. DEGs specific to the omental fat is significantly enriched in PPAR signaling pathway and cell-junction related pathway. In subcutaneous fat, cytokine-cytokine receptor interaction with chemokines (CXC and CC subfamily) was the most significantly enriched the pathways. Interestingly, melanogenesis pathway was associated with the subcutaneous depot. Even though the adipose tissues shared the same pathways for adipocyte differentiation, the regulation of genes were different based on the depot. *Conclusions: We comparatively analyzed the transcripome profile from different adipose tissues using NGS and identified DEGs between adipose depot and specific to depot in Hanwoo animals. The functional annotation analysis of DEGs found that transcriptome profile difference in various adipose tissue of intramuscular, subcutaneous, and ometal fat. whole mRNA sequencing profiles of nine Korean native cattle (nine profiles of omental fat tissue, nine profiles of intramuscular fat tissue, nine profiles of subcutaneous fat tissue and eight profiles of muscle tissue)
2013-07-25 | E-GEOD-39618 | biostudies-arrayexpress
Project description:Sympathetic activation during cold exposure increases adipocyte thermogenesis via the expression of mitochondrial protein uncoupling protein 1 (UCP1)1. The propensity of adipocytes to express UCP1 is under a critical influence of the adipose microenvironment and varies between sexes and among various fat depots2-7. Here, we report that cold-induced adipocyte UCP1 expression in a female mouse subcutaneous white adipose tissue (scWAT) is regulated by mammary gland ductal epithelial cells in the adipose niche. Single-cell RNA-sequencing (scRNA-seq) shows that glandular luminal epithelium subtypes express transcripts that encode secretory factors in controlling adipocyte UCP1 expression under cold conditions. We term luminal epithelium secretory factors as “mammokines”. Using whole-tissue immunofluorescence 3D visualization, we reveal previously undescribed sympathetic nerve-ductal points of contact. We show sympathetic nerve-activated mammary ducts limit adipocyte UCP1 expression via lipocalin 2. Both in vivo and ex vivo ablation of mammary ductal epithelium enhances cold-induced scWAT adipocyte thermogenic gene program. Since the mammary duct network extends throughout most scWATs in female mice, females show markedly less scWAT UCP1 expression, fat oxidation, energy expenditure, and subcutaneous fat mass loss compared to male mice, implicating sex-specific roles of mammokines in adipose thermogenesis. These results show a previously uncharacterized role of sympathetic nerve-activated glandular epithelium in adipocyte UCP1 expression and suggest an evolutionary function of mammary duct luminal cells in defending glandular adiposity during cold exposure. Overall, our findings highlight mammary gland epithelium as a highly active metabolic cell type and implicate a broader role of mammokines in controlling female adipose metabolism, mammary gland physiology, and systemic energy homeostasis.
2023-05-01 | GSE231394 | GEO
Project description:Case story. A patient with massive infiltration of the visceral adipose tissue depot by BAT in a patient with a catecholamine secreting paraganglioma. BAT tissue was identified by protein expression of UCP1 (western blotting and immunostaining) The goal of the study is to identify patterns of gene expression in BAT containing visceral fat compared to the patient's own subcutanous fat which did not express BAT. For comparison a pool of mRNA isolated from visceral fat from obese subjects was used. Patient Case, Gene expression array from a biopsy from the patient's visceral fat and a biopsy from the subcutaneous fat compared to one array of mRNA from the visceral depot pooled from a group of obese subjects
2014-08-12 | E-GEOD-49795 | biostudies-arrayexpress
Project description:Maternal nutrition during different stages of pregnancy can induce significant changes in the structure, physiology, and metabolism of the offspring. These changes could have important implications on food animal production especially if these perturbations impact muscle and adipose tissue development. The objective of this study was to evaluate the effect of different maternal diets on the transcriptome of fetal tissues in sheep. Ewes were bred to a single sire and from days 67 ± 3 of gestation until necropsy (days 130 ± 1), they were fed one of three isoenergetic diets: alfalfa haylage (H; fiber), corn (C; starch), or dried corn distillers grains (D; fiber plus protein plus fat). Longissimus dorsi (M), subcutaneous adipose depot (S), and perirenal adipose depot (R) tissues from individual fetuses were pooled and then analyzed by RNA sequencing. A total of 26 fetuses were removed from 15 dams. From the fetuses three different tissues were collected including one muscle, longissimus dorsi muscle (M), and two adipose tissues, perirenal adipose depot (R) and subcutaneous adipose depot (S). The RNA samples from the 26 fetuses were pooled to generate four biological replicates per maternal diet and tissue. In particular, per each diet and tissue, two RNA pools were created from male fetuses and two RNA pools were created from female fetuses. Overall, a total of 36 pools (i.e., 12 pools per tissue, 3 tissues in total) underwent RNA extraction, library generation, and subsequent sequencing.
2014-11-04 | E-GEOD-62938 | biostudies-arrayexpress
Project description:Brown adipose tissue (BAT) plays an essential role in metabolic homeostasis by dissipating energy via thermogenesis through uncoupling protein 1 (Ucp1). Previously, we reported that the TATA-binding protein Associated Factor 7L (Taf7l) is an important regulator of white adipose tissue (WAT) differentiation. Here, we show that Taf7l also serves as a molecular switch between brown fat and muscle lineages in vivo and in vitro. In adipose tissue, Taf7l containing TFIID complexes associate with PPAR to mediate DNA looping between distal enhancers and core promoter elements. Our findings suggest that presence of the tissue-specific Taf7l subunit in TFIID functions to promote long-range chromatin interactions during BAT lineage specification. mRNA-seq expression profiling wild type and Taf7l knockout interscapular brown adipose tissue (BAT)
2014-06-03 | E-GEOD-55797 | biostudies-arrayexpress
Project description:Objectives Intermittent fasting is an effective dietary intervention to combat metabolic disease. Here, we explore the adipose depot specific response to every-other-day fasting (EODF) in mice to identify mechanisms that underly the beneficial effects. Methods Male C57BL/6J mice were placed on a 12-day EODF or ad libitum diet, after which tissues were harvested including visceral (vWAT) and subcutaneous (scWAT) white adipose tissue, as well as brown adipose tissue (BAT), which was then analysed by unbiased mass spectrometry-based proteomics. Results After EODF treatment, pathway enrichment analysis of our dataset showed that both WAT depots showed increased mitochondrial protein content, with scWAT also showing increased UCP1, but mitochondrial protein content was decreased in BAT. This effect on mitochondria is correlated to the increased abundance of proteins involved in glycolysis, pyruvate metabolism, the TCA cycle and fatty acid synthesis in both WAT depots. Furthermore, EODF-treated mice downregulated the lipolysis pathway in vWAT including a 5-fold decrease in the abundance of the beta3 adrenergic receptor (ADRB3). Enrichment analysis lso revealed that vWAT of EODF treated mice had significantly reduced ECM proteins, which lowers the inflammatory potential of this organ. Our adipose depot proteomic survey also allowed us to identify depot-enriched protein expression, such as the vWAT enrichment for the AKAP12 protein related to PKA signalling that was down-regulated by EODF treatment. Conclusions These findings show how the adipose depots have adapted to the EODF regime to preserve the lipid store, with the most striking changes occurring in the vWAT depot to downregulate the lipolysis pathway and induce expression of pathways needed for fatty acid synthesis. This substrate cycling and reduced inflammatory potential of the adipose tissue may contribute to the improved insulin sensitivity observed in these animals.
2022-10-12 | PXD020255 | Pride
Project description:Various physiological stimuli, such as cold environment, diet, and hormones, trigger brown adipose tissue (BAT) to produce heat through sympathetic nervous system (SNS)- and -adrenergic receptors (ARs). The AR stimulation increases intracellular cAMP levels through heterotrimeric G proteins and adenylate cyclases, but the processes by which cAMP modulates brown adipocyte function are not fully understood. Here we described that specific ablation of cAMP production in brown adipocytes led to reduced lipolysis, mitochondrial biogenesis, uncoupling protein 1 (Ucp1) expression, and consequently defective adaptive thermogenesis. Elevated cAMP signaling by sympathetic activation inhibited Salt-inducible kinase 2 (Sik2) through protein kinase A (PKA)-mediated phosphorylation in brown adipose tissue. Inhibition of SIKs enhanced Ucp1 expression in differentiated brown adipocytes and Sik2 knockout mice exhibited enhanced adaptive thermogenesis at thermoneutrality in an Ucp1-dependent manner. Taken together, our data indicate that suppressing Sik2 by PKA-mediated phosphorylation is a requisite for SNS-induced Ucp1 expression and adaptive thermogenesis in BAT, and targeting Sik2 may present a novel therapeutic strategy to ramp up BAT thermogenic activity in humans.
2018-07-12 | PXD009262 | Pride
Project description:In the last decades, adipose tissue has been defined to play a central role in the control of energy balance. Furthermore, the proven endocrine and thermogenic functions of adipocytes have renewed interest in the study of this tissue, as the activation of non-shivering thermogenesis may hold great potential for the future treatment of obesity and T2D. Cold exposure has defined to activate this process. Here, the miRNA transcriptomic response of epididymal and inguinal white adipose depots (eWAT and iWAT, respectively) as well as that of the interscapular brown adipose depot (iBAT) of C57Bl/6 mice either exposed to 22ºC or 4ºC for the period of 4 days were examined. This in-detail study of the adaptation of each depot to cold exposure has allowed unraveling depot-specific regulatory molecular mechanisms.
2021-10-28 | E-MTAB-8966 | biostudies-arrayexpress