Genome-wide analysis of gene expression in brown adipose tissue (BAT) of mice lacking CD36.
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ABSTRACT: Analysis of gene expression in BAT lacking CD36. The hypothesis tested in the present study was that genes involved in lipid metabolism and mitochondrial function would be misregulated. Results provide important information about the role of CD36 in BAT.
Project description:Analysis of gene expression in BAT lacking CD36. The hypothesis tested in the present study was that genes involved in lipid metabolism and mitochondrial function would be misregulated. Results provide important information about the role of CD36 in BAT. Total RNA was obtained from the BAT of control and Cd36-/- mice subjected to an overnight fast.
Project description:Brown adipose tissue (BAT) was suggested to play an important role in lipid and glucose metabolism in rodents and possibly also in humans. In the current study, we used genetic and correlation analyses in the BXH/HXB recombinant inbred (RI) strains, derived from Brown Norway (BN) and spontaneously hypertensive rats (SHR), to identify genetic determinants of BAT function and its role in the pathogenesis of metabolic disturbances. Linkage analyses revealed significant quantitative trait locus (QTL) associated with interscapular BAT mass in the vicinity of the Cd36 (fatty acid translocase) gene on chromosome 4. Additional two closely linked QTL asociated with glucose oxidation and incorporation into BAT lipids were detected near the Wars2 (tryptophanyl tRNA synthetase 2, mitochondrial) candidate gene on chromosome 2.
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.
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
Project description:BAT obtained from embryos at E14.5, E15.5 or E16.5 of C57Bl6J mice used to prepare RNA which was then processed for analysis using MoGene-2_1-st Affymetrix microarrays according to standard procedures.
Project description:The interscapular brown adipose tissue (BAT) depots of adult male and female C57BL/6J mice, housed at 22 °C, were analyzed to identify sex differences in the BAT transcriptome at basal housing conditions.
Project description:Obesity and type 2 diabetes cause a loss in brown adipose tissue (BAT) activity in mice and human, but the molecular mechanisms that drive BAT cell remodeling remain largely. Using a multilayered approach, we comprehensively map a deep reorganization in the BAT cells. We uncovered a subset of macrophages as the lipid-associated macrophages (LAM), which were massively increased in genetic and dietary model of BAT expansion. LAM participate in this scenario by capturing extracellular vesicles carrying damaged lipids and mitochondria released from metabolically-stressed brown adipocytes. CD36 scavenger receptor drives LAM phenotype and through * in vitro* and *in vivo* models, we demonstrated that CD36-deficient LAM increased brown fat genes. LAM release Tgfb1 that reduces brown adipocytes identity through Aldh1a1 induction. This study provides the first description of cell dynamics in BAT of obese models identifying LAM as responder to tissue-level metabolic stress and key driver to loss of BAT cell identity.
Project description:Obesity and type 2 diabetes cause a loss in brown adipose tissue (BAT) activity in mice and human, but the molecular mechanisms that drive BAT cell remodeling remain largely. Using a multilayered approach, we comprehensively map a deep reorganization in the BAT cells. We uncovered a subset of macrophages as the lipid-associated macrophages (LAM), which were massively increased in genetic and dietary model of BAT expansion. LAM participate in this scenario by capturing extracellular vesicles carrying damaged lipids and mitochondria released from metabolically-stressed brown adipocytes. CD36 scavenger receptor drives LAM phenotype and through * in vitro* and *in vivo* models, we demonstrated that CD36-deficient LAM increased brown fat genes. LAM release Tgfb1 that reduces brown adipocytes identity through Aldh1a1 induction. This study provides the first description of cell dynamics in BAT of obese models identifying LAM as responder to tissue-level metabolic stress and key driver to loss of BAT cell identity.
Project description:Obesity and type 2 diabetes cause a loss in brown adipose tissue (BAT) activity in mice and human, but the molecular mechanisms that drive BAT cell remodeling remain largely. Using a multilayered approach, we comprehensively map a deep reorganization in the BAT cells. We uncovered a subset of macrophages as the lipid-associated macrophages (LAM), which were massively increased in genetic and dietary model of BAT expansion. LAM participate in this scenario by capturing extracellular vesicles carrying damaged lipids and mitochondria released from metabolically-stressed brown adipocytes. CD36 scavenger receptor drives LAM phenotype and through * in vitro* and *in vivo* models, we demonstrated that CD36-deficient LAM increased brown fat genes. LAM release Tgfb1 that reduces brown adipocytes identity through Aldh1a1 induction. This study provides the first description of cell dynamics in BAT of obese models identifying LAM as responder to tissue-level metabolic stress and key driver to loss of BAT cell identity.