Adipocyte Turnover: Relevance to Human Adipose Tissue Morphology

International audienceOBJECTIVE: Adipose tissue may contain few large adipocytes (hypertrophy) or many small adipocytes (hyperplasia). We investigated factors of putative importance for adipose tissue morphology. RESEARCH DESIGN AND METHODS: Subcutaneous adipocyte size and total fat mass were compared in 764 subjects with BMI 18-60 kg/m(2). A morphology value was defined as the difference between the measured adipocyte volume and the expected volume given by a curved-line fit for a given body fat mass and was related to insulin values. In 35 subjects, in vivo adipocyte turnover was measured by exploiting incorporation of atmospheric (14)C into DNA. RESULTS: Occurrence of hyperplasia (negative morphology value) or hypertrophy (positive morphology value) was independent of sex and body weight but correlated with fasting plasma insulin levels and insulin sensitivity, independent of adipocyte volume (beta-coefficient = 0.3, P < 0.0001). Total adipocyte number and morphology were negatively related (r = -0.66); i.e., the total adipocyte number was greatest in pronounced hyperplasia and smallest in pronounced hypertrophy. The absolute number of new adipocytes generated each year was 70% lower (P < 0.001) in hypertrophy than in hyperplasia, and individual values for adipocyte generation and morphology were strongly related (r = 0.7, P < 0.001). The relative death rate (approximately 10% per year) or mean age of adipocytes (approximately 10 years) was not correlated with morphology. CONCLUSIONS: Adipose tissue morphology correlates with insulin measures and is linked to the total adipocyte number independently of sex and body fat level. Low generation rates of adipocytes associate with adipose tissue hypertrophy, whereas high generation rates associate with adipose hyperplasia

DNPTrapper: an assembly editing tool for finishing and analysis of complex repeat regions

BACKGROUND: Many genome projects are left unfinished due to complex, repeated regions. Finishing is the most time consuming step in sequencing and current finishing tools are not designed with particular attention to the repeat problem. RESULTS: We have developed DNPTrapper, a shotgun sequence finishing tool, specifically designed to address the problems posed by the presence of repeated regions in the target sequence. The program detects and visualizes single base differences between nearly identical repeat copies, and offers the overview and flexibility needed to rapidly resolve complex regions within a working session. The use of a database allows large amounts of data to be stored and handled, and allows viewing of mammalian size genomes. The program is available under an Open Source license. CONCLUSION: With DNPTrapper, it is possible to separate repeated regions that previously were considered impossible to resolve, and finishing tasks that previously took days or weeks can be resolved within hours or even minutes

Database of Trypanosoma cruzi repeated genes: 20 000 additional gene variants

<p>Abstract</p> <p>Background</p> <p>Repeats are present in all genomes, and often have important functions. However, in large genome sequencing projects, many repetitive regions remain uncharacterized. The genome of the protozoan parasite <it>Trypanosoma cruzi </it>consists of more than 50% repeats. These repeats include surface molecule genes, and several other gene families. In the <it>T. cruzi </it>genome sequencing project, it was clear that not all copies of repetitive genes were present in the assembly, due to collapse of nearly identical repeats. However, at the time of publication of the <it>T. cruzi </it>genome, it was not clear to what extent this had occurred.</p> <p>Results</p> <p>We have developed a pipeline to estimate the genomic repeat content, where shotgun reads are aligned to the genomic sequence and the gene copy number is estimated using the average shotgun coverage. This method was applied to the genome of <it>T. cruzi </it>and copy numbers of all protein coding sequences and pseudogenes were estimated. The 22 640 results were stored in a database available online. 18% of all protein coding sequences and pseudogenes were estimated to exist in 14 or more copies in the <it>T. cruzi </it>CL Brener genome. The average coverage of the annotated protein coding sequences and pseudogenes indicate a total gene copy number, including allelic gene variants, of over 40 000.</p> <p>Conclusion</p> <p>Our results indicate that the number of protein coding sequences and pseudogenes in the <it>T. cruzi </it>genome may be twice the previous estimate. We have constructed a database of the <it>T. cruzi </it>gene repeat data that is available as a resource to the community. The main purpose of the database is to enable biologists interested in repeated, unfinished regions to closely examine and resolve these regions themselves using all available shotgun data, instead of having to rely on annotated consensus sequences that often are erroneous and possibly misleading. Five repetitive genes were studied in more detail, in order to illustrate how the database can be used to analyze and extract information about gene repeats with different characteristics in <it>Trypanosoma cruzi</it>.</p

Genome-wide investigation of in vivo EGR-1 binding sites in monocytic differentiation

A Genome-wide analysis of EGR-1 binding sites reveals co-localization with CpG islands and histone H3 lysine 9 binding. SP-1 binding occupancies near EGR-1 binding sites are dramatically altered

Transcriptional features of genomic regulatory blocks

CAGE tag mapping of transcription start sites across different human tissues shows that genomic regulatory blocks have unique features that are the likely cause of their ability to respond to regulatory inputs from very long distances

Genetic Predisposition for Type 2 Diabetes, but Not for Overweight/Obesity, Is Associated with a Restricted Adipogenesis

BACKGROUND: Development of Type 2 diabetes, like obesity, is promoted by a genetic predisposition. Although several genetic variants have been identified they only account for a small proportion of risk. We have asked if genetic risk is associated with abnormalities in storing excess lipids in the abdominal subcutaneous adipose tissue. METHODOLOGY/PRINCIPAL FINDINGS: We recruited 164 lean and 500 overweight/obese individuals with or without a genetic predisposition for Type 2 diabetes or obesity. Adipose cell size was measured in biopsies from the abdominal adipose tissue as well as insulin sensitivity (HOMA index), HDL-cholesterol and Apo AI and Apo B. 166 additional non-obese individuals with a genetic predisposition for Type 2 diabetes underwent a euglycemic hyperinsulinemic clamp to measure insulin sensitivity. Genetic predisposition for Type 2 diabetes, but not for overweight/obesity, was associated with inappropriate expansion of the adipose cells, reduced insulin sensitivity and a more proatherogenic lipid profile in non-obese individuals. However, obesity per se induced a similar expansion of adipose cells and dysmetabolic state irrespective of genetic predisposition. CONCLUSIONS/SIGNIFICANCE: Genetic predisposition for Type 2 diabetes, but not obesity, is associated with an impaired ability to recruit new adipose cells to store excess lipids in the subcutaneous adipose tissue, thereby promoting ectopic lipid deposition. This becomes particularly evident in non-obese individuals since obesity per se promotes a dysmetabolic state irrespective of genetic predisposition. These results identify a novel susceptibility factor making individuals with a genetic predisposition for Type 2 diabetes particularly sensitive to the environment and caloric excess

Ceruloplasmin is a novel adipokine which is overexpressed in adipose tissue of obese subjects and in obesity-associated cancer cells

Obesity confers an increased risk of developing specific cancer forms. Although the mechanisms are unclear, increased fat cell secretion of specific proteins (adipokines) may promote/facilitate development of malignant tumors in obesity via cross-talk between adipose tissue(s) and the tissues prone to develop cancer among obese. We searched for novel adipokines that were overexpressed in adipose tissue of obese subjects as well as in tumor cells derived from cancers commonly associated with obesity. For this purpose expression data from human adipose tissue of obese and non-obese as well as from a large panel of human cancer cell lines and corresponding primary cells and tissues were explored. We found expression of ceruloplasmin to be the most enriched in obesity-associated cancer cells. This gene was also significantly up-regulated in adipose tissue of obese subjects. Ceruloplasmin is the body's main copper carrier and is involved in angiogenesis. We demonstrate that ceruloplasmin is a novel adipokine, which is produced and secreted at increased rates in obesity. In the obese state, adipose tissue contributed markedly (up to 22%) to the total circulating protein level. In summary, we have through bioinformatic screening identified ceruloplasmin as a novel adipokine with increased expression in adipose tissue of obese subjects as well as in cells from obesity-associated cancers. Whether there is a causal relationship between adipose overexpression of ceruloplasmin and cancer development in obesity cannot be answered by these cross-sectional comparisons

Conserved temporal ordering of promoter activation implicates common mechanisms governing the immediate early response across cell types and stimuli

Conserved temporal precedence between IEGs (light blue nodes) and other protein-coding genes (green nodes) is shown by directed edges. Genes annotated with the GO term 'response to endoplasmic reticulum stress' (GO:003497) have a red rectangle around the gene name; red squares indicate genes with CAGE clusters enriched for XBP1 transcription factor binding sites