Project description:Visceral adipose tissue (VAT) is a metabolically active endocrine organ that plays a critical role regulating organismal metabolism. Regulatory T (Treg) cells restrain VAT inflammation, and preserve insulin sensitivity and organismal metabolism. Here we report pronounced sexual dimorphism in VAT Treg cells, which were enriched specifically in males and differed strikingly from their female counterparts in phenotype, transcriptional landscape and chromatin accessibility. These differences were imprinted by the adipose tissue in a manner dependent on sex hormones. Male VAT was characterized by heightened inflammation, which resulted in CCR2-dependent recruitment of Treg cells. Sex hormones also regulated the differentiation of unique IL-33-producing stromal cell populations specific to the male VAT, which paralleled the local expansion of Treg cells and the induction of a transcriptional program controlled by transcription factor Blimp1. Overall our findings reveal a novel multi-layered feedback circuit depending on Treg cells and regulated by sex hormones to limit VAT inflammation.
Project description:Visceral adipose tissue (VAT) is a metabolically active endocrine organ that plays a critical role regulating organismal metabolism. Regulatory T (Treg) cells restrain VAT inflammation, and preserve insulin sensitivity and organismal metabolism. Here we report pronounced sexual dimorphism in VAT Treg cells, which were enriched specifically in males and differed strikingly from their female counterparts in phenotype, transcriptional landscape and chromatin accessibility. These differences were imprinted by the adipose tissue in a manner dependent on sex hormones. Male VAT was characterized by heightened inflammation, which resulted in CCR2-dependent recruitment of Treg cells. Sex hormones also regulated the differentiation of unique IL-33-producing stromal cell populations specific to the male VAT, which paralleled the local expansion of Treg cells and the induction of a transcriptional program controlled by transcription factor Blimp1. Overall our findings reveal a novel multi-layered feedback circuit depending on Treg cells and regulated by sex hormones to limit VAT inflammation.
Project description:White adipose tissue (WAT) harbors functionally diverse subpopulations of adipose progenitor cells that differentially impact tissue plasticity in a sex- and depot-dependent manner. To date, the molecular basis of this cellular heterogeneity has not been fully defined. Here, we describe a multilayered omics approach to dissect adipose progenitor cell heterogeneity from in three dimensions: progenitor subpopulation, sex, and anatomical localization. We applied state-of-the-art mass spectrometry methods to quantify 4870 proteins in eight different stromal cell populations from perigonadal and inguinal WAT of male and female mice and acquired transcript expression levels of 15477 genes using RNA-seq. Notably, our data highlight the molecular signatures defining sex differences in PDGFR+ preadipocyte differentiation and identify regulatory pathways that functionally distinguish adipose tissue PDGFRb+ subpopulations. The data are freely accessible as a resource at "Pread Profiler. Together, the multilayered omics analysis provides unprecedented insights into adipose stromal cell heterogeneity.
Project description:ATAC-seq on human adipose tissue For data usage terms and conditions, please refer to http://www.genome.gov/27528022 and http://www.genome.gov/Pages/Research/ENCODE/ENCODE_Data_Use_Policy_for_External_Users_03-07-14.pdf
Project description:Both epidemiological data and scientific reports corroborate the higher incidence ofneuropathy and chronic pain in female gender not only in patients with metabolicdisorders but also in normometabolic subjects and in murine models. Our previousresults showed different immune and neuroimmune response to neuropathic pain(NeP) between male and female mice as well as a different metabolic pattern inproteins expressed in sciatic nerve. Here, we provide evidence that adipose tissue(AT) plays a contributing role in sex-dependent differences before and after peripheralnerve injury-induced NeP in mice. The metabolic parameters assessed, the metabolicprofile signature (metabolomics), the energy expenditure evaluation, the AT proteomicanalysis and the adipokines mobilization reveal a sex-specific AT response toperipheral nerve damage. Of interest, an alteration of lipolysis and fatty acids oxidation(FAO) emerges in females as well as an enhancement of whole-body energyexpenditure and higher secretion of sex hormones from AT, affecting glucose andinsulin metabolism. On the contrary, neuropathy in males induced an engagement ofglycolysis pathway, a decrease of systemic energy expenditure and unsaturated fattyacids levels. In males, AT responds favoring molecules useful in regenerativeprocesses and in the oxidative stress, as well as stimulating peroxisome proliferatoractivated receptors (PPARs) gamma subtype (PPAR-γ) and adiponectin.This study discloses new factors underlying the higher susceptibility of female sex toNeP, indicating in AT a crucial player for the regulation of sex-dependent inflammatoryand metabolic response to nerve lesion.