Effects of acute loss of mature adipocytes in adipose tissue on the liver
Ontology highlight
ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE227966 | GEO | 2023/04/18
REPOSITORIES: GEO
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Project description:We previously demonstrated that antisense oligonucleotide (ASO)-mediated knockdown of Mboat7, the gene encoding Membrane Bound O-Acyltransferase 7, in the liver and adipose tissue of mice promoted high fat diet-induced hepatic steatosis, hyperinsulinemia, and systemic insulin resistance. Thereafter, other groups showed that hepatocyte-specific genetic deletion of Mboat7 promoted striking fatty liver and NAFLD progression in mice but does not alter insulin sensitivity, suggesting the potential for cell autonomous roles. Here, we show that MBOAT7 function in adipocytes contributes to diet-induced metabolic disturbances including hyperinsulinemia and systemic insulin resistance. We generated floxed Mboat7 mice and created hepatocyte- and adipocyte-specific knockout mice using Cre-recombinase mice under the control of the albumin and adiponectin promoter, respectively. After chow and high fat diet feeding (60% kCal fat), mice were subjected to metabolic phenotyping and tissues to molecular workup and analysis. Here, we show that MBOAT7 function in adipocytes contributes to diet-induced metabolic disturbances including hyperinsulinemia and systemic insulin resistance. The expression of Mboat7 in white adipose tissue closely correlates with diet-induced obesity across a panel of ~100 inbred strains of mice fed a high fat/high sucrose diet. Moreover, we found that adipocyte-specific genetic deletion of Mboat7 is sufficient to promote hyperinsulinemia, systemic insulin resistance, and mild fatty liver. Unlike in the liver, where Mboat7 plays a relatively minor role in maintaining arachidonic acid (AA)-containing PI pools, Mboat7 is the major source of AA-containing PI pools in adipose tissue. Our data demonstrate that MBOAT7 is a critical regulator of adipose tissue PI homeostasis, and adipocyte MBOAT7-driven PI biosynthesis is closely linked to hyperinsulinemia and insulin resistance in mice.
2023-05-10 | PXD039894 | Pride
Project description:We have identified a population of adipocytes in fat tissue that arise from bone marrow-derived progenitor cells. We used microarrays to compare the global gene expression patterns of the bone marrow progenitor-derived adipocytes as well as conventional white and brown adipocytes to evaluate the relationship between these adipocyte subpopulations. Gonadal fat tissue (for white adipocytes) and intrascapular fat tissue (for brown adipocytes) was digested with collagenase and adipocytes were recovered by centrifugation/flotation. Bone marrow derived adipocytes were isolated from the adipocyte fraction of gonadal fat tissue from mice receiving bone marrow tranplants from donors expressing either green fluorescent protein (GFP) or beta-galactosidase (LacZ) by flow cytometry.
2010-01-08 | E-GEOD-19757 | biostudies-arrayexpress
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2023-04-18 | GSE227967 | GEO
Project description:The CCR4-NOT deadenylase complex has a critical function to trigger mRNA decay and various biological events. To understand roles of the complex in adipocyte function, we compare mRNA half-lives between control and Cnot complex-deficient mature adipocytes from iWAT and BAT.
2019-10-24 | E-MTAB-8371 | biostudies-arrayexpress
Project description:We took a systematic approach to determine the transcriptional programs that are specifically regulated by C/EBP? in mature white adipocytes of mice on chow diet or high fat diet. The hypothesis tested in the present study was that C/EBP?, as a lipogenic transcription factor, has unique direct targets compared to PPAR?. Our inducible adipocyte specific knockout system allows us to test the direct targets of C/EBP? and PPAR? in adipocytes by short-term C/EBP? or PPAR? elimination in mature adipocytes in vivo. Results indicate that although it has been shown that C/EBP? and PPAR? cross-regulate each other, they have distinct direct responsive targets. Moreover, there are very few C/EBP? specific targets in mice on a chow diet, most of the C/EBP? targets in mature adipocytes are genes modulated by HFD feeding. Total RNA obtained from subcutaneous adipose tissue of Adn-C/EBP?-/- mice on doxycycline chow diet for 3 days, doxycycline high fat diet for 3 days or 1 month and Adn-PPAR?-/- mice on doxycycline chow diet for 3 days, compared to control littermates.
2014-11-04 | E-GEOD-62937 | biostudies-arrayexpress
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2023-01-14 | E-MTAB-12498 | biostudies-arrayexpress
Project description:We took a systematic approach to determine the transcriptional programs that are specifically regulated by C/EBPα in mature white adipocytes of mice on chow diet or high fat diet. The hypothesis tested in the present study was that C/EBPα, as a lipogenic transcription factor, has unique direct targets compared to PPARγ. Our inducible adipocyte specific knockout system allows us to test the direct targets of C/EBPα and PPARγ in adipocytes by short-term C/EBPα or PPARγ elimination in mature adipocytes in vivo. Results indicate that although it has been shown that C/EBPα and PPARγ cross-regulate each other, they have distinct direct responsive targets. Moreover, there are very few C/EBPα specific targets in mice on a chow diet, most of the C/EBPα targets in mature adipocytes are genes modulated by HFD feeding.
2014-11-04 | GSE62937 | GEO
Project description:Obesity is considered as a major public health concern with strong economic and social burdens. Exposure to pollutants such as heavy metals can contribute to the development of obesity and its associated metabolic disorders, including type 2 diabetes and cardiovascular diseases. Adipose tissue is an endocrine and paracrine organ that plays a key role in the development of these diseases and is one of the main target of heavy metal accumulation. In this study, we determined by inductively coupled plasma mass spectrometry cadmium concentrations in human subcutaneous and visceral adipose tissues, ranging between 2.5 nM and 2.5 µM. We found a positive correlation between cadmium levels and age, sex and smoking status and a negative correlation between cadmium and body mass index. Based on cadmium adipose tissue concentrations found in humans, we investigated the effects of cadmium exposure, at concentrations between 1 nM and 10 µM, on adipose-derived human mesenchymal stem cells differentiated into mature adipocytes in vitro. Transcriptomic analysis highlighted that such exposure altered the expression of genes involved in trace element homeostasis and heavy metal detoxification, such as Solute Carrier Family transporters and metallothioneins. This effect correlated with zinc level alteration in cells and cellular media. Interestingly, dysregulation of zinc homeostasis and transporters has been particularly associated with the development of obesity and type 2 diabetes. Moreover, we found that cadmium exposure induces the pro-inflammatory state of the adipocytes by enhancing the expression of genes such as IL-6, IL-1B and CCL2, cytokines also induced in obesity. Finally, cadmium modulates various adipocyte functions such as the insulin response signaling pathway and lipid homeostasis. Collectively, our data identified some of the cellular mechanisms by which cadmium alters adipocyte functions, thus highlighting new facets of its potential contribution to the progression of metabolic disorders.
2023-06-29 | MTBLS4128 | MetaboLights
Project description:Lipid overload and adipocyte dysfunction are key to the development of insulin resistance and can be induced by a high-fat diet. CD1d-restricted invariant natural killer T (iNKT) cells have been proposed as mediators between lipid overload and insulin resistance, but recent studies found decreased iNKT cell numbers and marginal effects of iNKT cell depletion on insulin resistance under high-fat diet conditions. Here, we focused on the role of iNKT cells under normal conditions. We showed that iNKT cell–deficient mice on a low-fat diet, considered a normal diet for mice, displayed a distinctive insulin resistance phenotype without overt adipose tissue inflammation. Insulin resistance was characterized by adipocyte dysfunction, including adipocyte hypertrophy, increased leptin, and decreased adiponectin levels. The lack of liver abnormalities in CD1d-null mice together with the enrichment of CD1d-restricted iNKT cells in both mouse and human adipose tissue indicated a specific role for adipose tissue–resident iNKT cells in the development of insulin resistance. Strikingly, iNKT cell function was directly modulated by adipocytes, which acted as lipid antigen-presenting cells in a CD1d-mediated fashion. Based on these findings, we propose that, especially under low-fat diet conditions, adipose tissue–resident iNKT cells maintain healthy adipose tissue through direct interplay with adipocytes and prevent insulin resistance. four samples
2012-08-06 | E-GEOD-39534 | biostudies-arrayexpress
Project description:Recents studies in mice and humans demonstrated the relevance of H2S-synthesising enzymes (such as CTH, CBS and MPST) in adipose tissue physiology and preadipocyte differentiation into adipocytes. Here, we aimed to investigate the combined role of CTH, CBS and MPST in the preservation of adipocyte protein persulfidation and adipogenesis. Joint CTH, CBS and MPST gene knockdown was achieved treating fully human adipocytes with siRNAs against these transcripts (siRNA_MIX). Adipocyte protein persulfidation was analyzed by a mass spectrometry label-free quantitative approach coupled with a dimedone-switch method for protein labeling and purification. The proteomic analysis quantified 216 proteins with statistically different persulfidation levels in KD cells compared to control adipocytes. In fully differentiated adipocytes, CBS and MPST mRNA and protein levels were abundant, whereas CTH expression was very low. Of note, siRNA_MIX administration resulted in a significant decrease in CBS and MPST expression, without impacting on CTH. Dual CBS and MPST gene knockdown resulted in decreased expression of relevant genes for adipocyte biology, including adipogenesis, mitochondrial biogenesis and lipogenesis, but increased proinflammatory- and senescence-related genes, in parallel to a significant disruption in adipocyte protein persulfidation pattern. While among less persulfidated proteins, we identified several relevant proteins for adipocyte adipogenesis and function, among the most persulfidated, key mediators of adipocyte inflammation and dysfunction, but also some proteins that might have a positive role of adipogenesis were found. In conclusion, current study indicates that joint knockdown of CBS and MPST (but not CTH) in adipocytes impairs adipogenesis and promotes inflammation, possibly by disrupting the pattern of protein persulfidation in these cells, and suggesting that these enzymes were required for the functional maintenance of adipocytes.
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