Project description:The preadipocytes’ shape changes dramatically during differentiation, in parallel with lipid accumulation and cytoskeletal reorganization. Failure to do so may impact the flexibility of adipose tissue (AT) to shift between lipid storage and mobilization, leading to impaired metabolism and insulin resistance. Transgelin 2 (TAGLN2) was identified as a cytoskeletal protein expressed in AT and associated with obesity and inflammation both in mice and humans, being normalized upon weight loss. Tagln2 knockdown in preadipocytes revealed a key functional role, being required for proliferation and biosynthetic and oxidation pathways. The phenotype of gain of function in vivo (aP2-Tagln2 mice) disclosed important gender-related differences, in whom transgenic female mice over-expressing Tagln2 in AT exhibited “healthy” obesity, characterized by increased fat mass, hypertrophic adipocytes, and preserved insulin sensitivity. Conversely, transgenic males exhibited enhanced activation of T helper cells, mitochondrial dysfunction, and impaired fatty acid metabolism in AT, together with decreased insulin sensitivity and the prevalence of small adipocytes, suggestive of defective AT expandability. The metabolic relevance of TAGLN2 in humans was supported by the existence of single nucleotide polymorphisms that can modulate TAGLN2 gene expression in AT and are associated with obesity and protection from ischemic heart disease in GWAS public databases. Collectively, current findings highlight the contribution of cytoskeletal TAGLN2 to AT expansion and protection from cardiometabolic disease in a gender-dependent manner.
Project description:Analysis of the effect on global gene regulation in epididymal adipose tissue of overexpressing the cytoskeletal tropomyosin, Tm5NM1 to help understand the transcriptional events that lead to increased fat mass in transgenic mice. Total RNA obtained from epididymal adipose tissue for 3 month old transgenic and non-transgenic control mice.
Project description:Analysis of the effect on global gene regulation in epididymal adipose tissue of overexpressing the cytoskeletal tropomyosin, Tm5NM1 to help understand the transcriptional events that lead to increased fat mass in transgenic mice.
Project description:Introduction: The human adipose tissue proteome associated with type 2 diabetes (DM) is not well described. An understanding of the DM-specific adipose tissue proteome would provide insight into mechanisms underlying the pathogenesis of DM.
Methods: We used label-free proteomics analysis to quantify differences between visceral adipose tissue samples from obese women with and without DM.
Results: 2640 protein groups were identified and 1965 were subject to statistical analysis. 23 were differently abundant between groups (q < 0.1, moderated t-test, n = 10). Proteins localized to the mitochondria or involved in mitochondrial functions including the TCA cycle and fatty acid metabolism were decreased in abundance in samples from women with DM relative to NDM samples while proteins involved in cytoskeletal function and innate inflammatory signaling pathways were increased.
Conclusion: The visceral adipose tissue proteome in DM is characterized by defects in mitochondrial function, TCA metabolism, inflammation and immunity, and cytoskeletal function. Alterations in the levels of specific proteins associated with these pathways provide insight into mechanisms of adipose tissue dysfunction in the context of metabolic disease.
Project description:Gender dependent gene expression in the kidney of 36 day old rats using the Affymetrix GeneChip rat expression set 230 array RAE230A. mixed model ANOVA using log2 transformed signal intensity of PM. Keywords: repeat Three rat strains Mhm, Us and MhmBN were examined. Three arrays were performed for each gender and strain combination. Total RNA from three rats was pooled for each array.
Project description:Obesity is a major risk factor for a high number of secondary diseases, including cancer. Specific insights into the role of gender differences and secondary co-morbidities, such as type 2 diabetes (T2D) and cancer risk, are yet to be fully obtained. The aim of this study is thus to find a correlation between the transcriptional deregulation present in the subcutaneous adipose tissue of obese patients and the risk of cancer, in the presence of T2D, and considering gender differences. Through deep RNA-sequencing we highlighted the presence of both coding and non-coding deregulated RNAs, and we subsequently assessed their oncogenic risk. We correlated the oncogenes with anthropometrical parameters, highlighting significant trends. For each analysed condition we assessed the oncogenic pathways deregulated, the specific prognosis for different cancer types and the lncRNAs involvement in oncogenic networks and tissues. Our results provided a comprehensive characterization of oncogenesis correlation in subcutaneous adipose tissue, providing specific insights into the oncogenic prognosis for obese, diabetic or gender-specific differences. These results could shed light on new molecular targets to be specifically modulated in obesity and highlight which cancers should be most looked out for a better prevention in obesity affected patients.
Project description:Gender dependent gene expression in the kidney of 36 day old rats using the Affymetrix GeneChip rat expression set 230 array RAE230A. mixed model ANOVA using log2 transformed signal intensity of PM. Keywords: repeat
Project description:Adipose tissue gene expression was profiled from perigonadal adipose tissue of mice whose body mass and insulin sensitivity varied as a function of diet, gender, monogenic mutations and insulin sensitizing therapies. Mice were 22-24 weeks of age and sacrificed between 2-3 hours into the light portion of a 12/12 dark-light cycle. The goal was to identify transcripts whose adipose tissue expression is correlated with adiposity, insulin sensitivity and other measures of metabolic function. Keywords: population
Project description:Background: Adipose tissue-derived stromal cells (ATSCs) hold great promises in regenerative medicine, due to their easy retrieval, high proliferative capacity, and multi-lineage differentiation potential. In the last decade, several studies have reported the plasticity of ATSCs toward a hepatic fate. Nonetheless, the molecular mechanisms underlying the conversion from a mesenchymal to an epithelial phenotype remain poorly understood. Aim: In this study, we compared the full genome expression profiles of ATSCs cultured for 4 weeks under pro-hepatogenic conditions to undifferentiated ATSCs, in order to depict the molecular events involved in ATSC hepatic transdifferentiation. Methods: Molecular analysis was performed using the Affymetrix human focus arrays. Sets of differentially expressed genes were functionally categorized in order to understand which pathways drive the hepatic conversion and interesting target genes were validated by Q-PCR. Results: We showed that ATSC-derived hepatocyte-like cells activate several genes associated with specific liver functions, including protein metabolism, innate immune response regulation, and biodegradation of toxic compounds. Furthermore, microarray analysis highlighted the downregulation of several transcripts involved in stemness maintenance along with genes associated with a mesenchymal phenotype. Conclusion: Taken together, our data suggest that the in vitro system used in this study drove ATSCs toward a hepatic conversion through a subtle regulation of molecular pathways controlling stem cell properties and lineage commitment that promote mesenchymal-epithelial-transition. Adipose tissue was obtained from 3 patients undergoing partial abdominoplasty. Adipose tissue-derived stromal cells (ATSC) were isolated according to standard procedures, using the in vitro adherence property of these cells. At passage culture 4, ATSC were submitted to an in vitro hepatogenic regimen, consisting of the sequential addition of growth factors. After 1 month of in vitro differentiation, cells were harvested and their transcriptome was compared to control ATSC.