DCHP targets lipid associated macrophages to disrupt lipid metabolism via crosstalk with adipocyte precursor cells
Ontology highlight
ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE246564 | GEO | 2024/11/01
REPOSITORIES: GEO
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Project description:Suboptimal intrauterine nutrition predisposes the fetus to central obesity and metabolic syndrome in adult life, suggesting nutritional programming of the fat distribution. However, the underlying mechanisms are not elucidated. We hypothesized that prenatal nutritional deprivation leads to stimulation of adipogenesis, as an adaptive mechanism, in a depot-dependent manner. The induction of adipogenesis is most enhanced in the subcutaneous lower-body depots, followed by the subcutaneous upper-body and visceral adipose tissue depots. Stimulation of adipogenesis may lead to an early consumption of the stem cell pool, and thus, may impair adipose tissue expandability postnatally, which may lead to differences in regional adipose tissue growth. We tested this hypothesis by analyzing global gene expression to identify expression patterns in subcutaneous abdominal, subcutaneous femoral, and omental adipose depots of baboon fetuses that have been altered by nutritional maternal deprivation. Adipose tissue was collected from baboon fetuses at 165 dG from mothers fed control or 30% nutrient-restricted diets (three females and one male in each group). 24 samples, each consisted of pooled total RNA from triplicate wells (6-well plate).
2011-12-16 | E-GEOD-34464 | biostudies-arrayexpress
Project description:Suboptimal intrauterine nutrition predisposes the fetus to central obesity and metabolic syndrome in adult life, suggesting nutritional programming of the fat distribution. However, the underlying mechanisms are not elucidated. We hypothesized that prenatal nutritional deprivation leads to stimulation of adipogenesis, as an adaptive mechanism, in a depot-dependent manner. The induction of adipogenesis is most enhanced in the subcutaneous lower-body depots, followed by the subcutaneous upper-body and visceral adipose tissue depots. Stimulation of adipogenesis may lead to an early consumption of the stem cell pool, and thus, may impair adipose tissue expandability postnatally, which may lead to differences in regional adipose tissue growth. We tested this hypothesis by analyzing global gene expression to identify expression patterns in subcutaneous abdominal, subcutaneous femoral, and omental adipose depots of baboon fetuses that have been altered by nutritional maternal deprivation. Adipose tissue was collected from baboon fetuses at 165 dG from mothers fed control or 30% nutrient-restricted diets (three females and one male in each group).
2011-12-16 | GSE34464 | GEO
Project description:Background and aims: Metabolic diseases, including diabetes, obesity, and dyslipidemia, are significant public health concerns worldwide. The insulin-like growth factor 2 (IGF2) gene have been implicated in various physiological processes, but its specific role in lipid metabolism remains unclear. We aim to elucidate the role of IGF2 in regulating lipid metabolism in adipose tissues and its association with metabolic syndrome (MetS). Methods: The research employed a multidisciplinary approach to investigate the role of IGF2 in lipid metabolism. We investigated the correlation between genetic variations within the IGF2 gene and metabolic parameters. We conduct a cross-sectional human study to evaluate relationships between varying IGF2 serum concentrations and the incidence of MetS. Additionally, manipulation of IGF2 expression levels in mouse and cell models via overexpression and knockdown to assess impacts on lipid metabolism in adipose tissue, specifically lipid accumulation, insulin resistance, and the balance between lipogenesis and lipolysis. Furthermore, the study employs metabolomics techniques to scrutinize the broader metabolic profiles in adipose tissues in response to IGF2 modulation. Results: Multiple SNP loci in the IGF2 gene were significantly associated with BMI, HbA1c, and diabetes. Insufficient or excessive expression of IGF2 was identified as a risk factor for hyperlipidemia, low HDL-c, and central obesity in MetS. We observed that IGF2 was mainly concentrated in adipose tissues and adipocytes. Enhanced IGF2 expression stimulated adipogenesis and lipid accumulation, whereas IGF2 knockdown hindered lipolysis, exacerbating ectopic lipid accumulation and insulin resistance. There is a substantial enlargement of pancreatic tissue and heightened insulin generation in mice deficient in IGF2. Activation of the PI3K/Akt pathway through IGF1R in IGF2 excess or INSR in conditions of IGF2 scarcity, along with inhibition of AMPK, implies a common downstream process that favors lipid accumulation and metabolic reprogramming in adipocytes. Conclusions: Our study demonstrated that upregulation of IGF2 enhanced adipogenesis and lipogenesis, while knockdown of IGF2 inhibited lipolysis, which resulting in accelerating lipid accumulation through PI3K/Akt-AMPK pathway.
2024-08-08 | GSE273546 | GEO
Project description:Bariatric surgery is the most effective therapy of severe human obesity. It is associated with improvements in metabolic and non metabolic co-morbidities which are thought to be mediated by a decrease of adipose tissue inflammation. However, the molecular mechanisms behind these beneficial effects are poorly understood. We analyzed expression profiles in subcutaneous adipose tissue from 22 obese women before and 3 months after surgery using the RNA-seq technology. Of 15,972 detected genes, 1214 were differentially expressed after surgery. Upregulated genes were mostly involved in the basal cellular machinery. Downregulated genes were enriched in metabolic functions of adipose tissue. At baseline, we identified 26 modules of coexpressed genes. The four most stable modules reflected the innate and adaptive immune responses of adipose tissue, including a general signature of innate immune cells, an adaptive immune response elicited by T lymphocytes, a neutrophil-mediated inflammatory signature and an interferon-signaling pathway, respectively. After surgery, a few crucial molecules involved in chemotaxis and activation of immune cells were disconnected from their respective networks. These molecules may represent therapeutic targets against adipose inflammation. mRNA sequencing of subcutaneous adipose tissue (SAT) samples from 22 obese women before and 3 months after bariatric surgery
2015-03-31 | E-GEOD-65540 | biostudies-arrayexpress
Project description:Obesity is an energy balance disorder in which nutrient intake chronically exceeds energy expenditure, resulting in the accumulation of white adipose tissue. Increased adiposity is due to increases in the number and size of adipocytes, which leads to increased body fat and metabolic consequences. Adipocytes induce insulin resistance by promoting lipotoxicity and modulating adipokine secretion. Therefore, a thorough understanding of the mechanisms that regulate adipogenesis could have clinical relevance in preventing and treating obesity and the metabolic syndrome. In this study, we performed miRNA array to measure miRNA profiles of undifferentiated and differentiated 3T3-L1 adipocytes using Agilent(r) miRNA array. We show that miRNA profile changes during adipogenesis. Thus, this data would be useful to find the distinct role of miRNAs for the regulation of adipogenesis.
2013-08-07 | E-MTAB-1783 | biostudies-arrayexpress
Project description:Obesity is linked to the development of metabolic disorders. Expansion of white adipose tissue (WAT) from hypertrophy of pre-existing adipocytes and/or differentiation of precursors into new mature adipocytes contributes to obesity. We found that Nck2 expression is largely restricted to WAT, raising the hypothesis that it may play a unique function in that tissue. Using mice lacking Nck2, we found that Nck2 regulates adipocyte hypertrophy thus contributing to increased adiposity and progressive glucose intolerance, insulin resistance and hepatic steatosis. These findings were recapitulated in humans such that Nck2 expression in omental WAT was inversely correlated with the degree of obesity. Mechanistically, Nck2 deficiency promoted the induction of an adipocyte differentiation program and signaling by the PERK-eIF2α-ATF4 pathway in agreement with a role for the unfolded protein response in adipogenesis. These findings uncover Nck2 as a novel regulator of adipogenesis and that perturbation in its functionality contributes to adiposity-related metabolic disorders. Differential gene expression profile between epididymal white adipose tissue of Nck2-/- and Nck2+/+ mice by RNA sequencing (Illumina HiSEq 2000)
2016-07-01 | E-GEOD-63510 | biostudies-arrayexpress
Project description:Adipose tissue abundance relies partly on the factors that regulate adipogenesis, i.e. proliferation and differentiation of adipocytes. While the transcriptional program that initiates adipogenesis is well-known, the importance of microRNAs in adipogenesis is less well studied. We thus set out to investigate whether miRNAs would be actively modulated during adipogenesis and obesity. Several models exist to study adipogenesis in vitro, of which the cell line 3T3-L1 is probably the most well known, albeit not the most physiologically appropriate. We used a microarray strategy to provide a global profile of miRNAs in brown and white primary murine adipocytes (prior to and following differentiation) and evaluated the similarity of the responses to non-primary cell models, through literature data-mining. We found 65 miRNAs regulated during in vitro adipogenesis in primary adipocytes. When we compared our primary adipocyte profiles with those of cell lines reported in the literature, we found a high degree of difference in adipogenesis-regulated miRNAs. We evaluated the expression of 10 of our adipogenesis-regulated miRNAs using real-time qPCR and then selected 5 miRNAs that showed robust expression levels and profiled these by qPCR in subcutaneous adipose tissue of 20 humans with a range of body mass indices (BMI, range=21-48). Of the miRNAs tested, mir-21 was both highly expressed in human adipose tissue and positively correlated with BMI (R2=0.49, p<0.001). In conclusion, we provide the preliminary analysis of miRNAs important for primary cell in vitro adipogenesis and find that the inflammation-associated miRNA, mir-21, is up-regulated in subcutaneous adipose tissue in human obesity. 3 samples of pre adipocytes isolated from brown adipose tissue examined pre and post differentiation to brown adipocytes. 3 samples of pre-adipocytes isolated from white adipose tissue and examined pre and post differentiation to adipocytes.
2011-05-31 | E-GEOD-27912 | biostudies-arrayexpress
Project description:Immune cells residing in white adipose tissue have been highlighted as important factors contributing to the pathogenesis of metabolic diseases, but the molecular regulators that drive adipose tissue immune cell remodeling during obesity remain largely unknown. Using index and transcriptional single-cell sorting, we comprehensively map all adipose tissue immune populations in both mice and humans during obesity. We describe a novel and conserved Trem2+ lipid-associated macrophage (LAM) subset and identify markers, spatial localization, and functional pathways associated with these cells. Genetic ablation of Trem2 in mice globally inhibits the downstream LAM molecular program during obesity, leading to adipocyte hypertrophy and both tissue-level and systemic hypercholesterolemia and glucose intolerance. These findings identify Trem2 signaling as a major pathway by which macrophages respond to loss of tissue-level lipid homeostasis, highlighting Trem2 as a key sensor of metabolic pathologies across multiple tissues and a potential therapeutic target in metabolic diseases.
2019-06-27 | GSE128518 | GEO
Project description:The adaptive mechanisms in response to excess energy supply are still poorly known in humans. Our aims were to define metabolic responses and changes in gene expression in adipose tissue of healthy volunteers during fat overfeeding. Healthy lean and overweight subjects were submitted to a high fat diet during 56 days. Adipose tissue biopsies were taken at Day 0, Day 14 and Day 56.
2012-03-05 | E-GEOD-28005 | biostudies-arrayexpress
Project description:Adipose tissue abundance relies partly on the factors that regulate adipogenesis, i.e. proliferation and differentiation of adipocytes. While the transcriptional program that initiates adipogenesis is well-known, the importance of microRNAs in adipogenesis is less well studied. We thus set out to investigate whether miRNAs would be actively modulated during adipogenesis and obesity. Several models exist to study adipogenesis in vitro, of which the cell line 3T3-L1 is probably the most well known, albeit not the most physiologically appropriate. We used a microarray strategy to provide a global profile of miRNAs in brown and white primary murine adipocytes (prior to and following differentiation) and evaluated the similarity of the responses to non-primary cell models, through literature data-mining. We found 65 miRNAs regulated during in vitro adipogenesis in primary adipocytes. When we compared our primary adipocyte profiles with those of cell lines reported in the literature, we found a high degree of difference in adipogenesis-regulated miRNAs. We evaluated the expression of 10 of our adipogenesis-regulated miRNAs using real-time qPCR and then selected 5 miRNAs that showed robust expression levels and profiled these by qPCR in subcutaneous adipose tissue of 20 humans with a range of body mass indices (BMI, range=21-48). Of the miRNAs tested, mir-21 was both highly expressed in human adipose tissue and positively correlated with BMI (R2=0.49, p<0.001). In conclusion, we provide the preliminary analysis of miRNAs important for primary cell in vitro adipogenesis and find that the inflammation-associated miRNA, mir-21, is up-regulated in subcutaneous adipose tissue in human obesity. A global transcriptomic survey of subcutaneous adipose tissue from human subjects characterised as having normal glucose tolerance, glucose intolerance or frank type 2 diabetes.
2011-05-31 | E-GEOD-27949 | biostudies-arrayexpress