scholarly journals Differential Subcutaneous Adipose Tissue Gene Expression Patterns in a Randomized Clinical Trial of Efavirenz or Lopinavir-Ritonavir in Antiretroviral-Naive Patients

2014 ◽  
Vol 58 (11) ◽  
pp. 6717-6723 ◽  
Author(s):  
L. Egaña-Gorroño ◽  
E. Martínez ◽  
P. Domingo ◽  
M. Loncà ◽  
T. Escribà ◽  
...  

ABSTRACTGene expression studies of subcutaneous adipose tissue may help to better understand the mechanisms behind body fat changes in HIV-infected patients who initiate antiretroviral therapy (ART). Here, we evaluated early changes in adipose tissue gene expression and their relationship to fat changes in ART-naive HIV-infected patients randomly assigned to initiate therapy with emtricitabine/tenofovir plus efavirenz (EFV) or ritonavir-boosted lopinavir (LPV/r). Patients had abdominal subcutaneous adipose tissue biopsies at baseline and week 16 and dual-energy-X-ray absorptiometry at baseline and weeks 16 and 48. mRNA changes of 11 genes involved in adipogenesis, lipid and glucose metabolism, mitochondrial energy, and inflammation were assessed through reverse transcription-quantitative PCR (RT-qPCR). Additionally, correlations between gene expression changes and fat changes were evaluated. Fat increased preferentially in the trunk with EFV and in the limbs with LPV/r (P< 0.05). After 16 weeks of exposure to the drug regimen, transcripts ofCEBP/A,ADIPOQ,GLUT4,LPL, andCOXIVwere significantly down-regulated in the EFV arm compared to the LPV/r arm (P< 0.05). Significant correlations were observed betweenLPLexpression change and trunk fat change at week 16 in both arms and betweenCEBP/AorCOXIVchange and trunk fat change at the same time point only in the EFV arm and not in the LPV/r arm. When combined with emtricitabine/tenofovir as standard backbone therapy, EFV and LPV/r induced differential early expression of genes involved in adipogenesis and energy metabolism. Moreover, these mRNA expression changes correlated with trunk fat change in the EFV arm. (This was a substudy of a randomized clinical trial [LIPOTAR study] registered atClinicalTrials.govunder identifier NCT00759070.)

Obesity ◽  
2012 ◽  
Vol 20 (11) ◽  
pp. 2168-2173 ◽  
Author(s):  
Charles W. Rehrer ◽  
Anis Karimpour-Fard ◽  
Teri L. Hernandez ◽  
Christopher K. Law ◽  
Nichole R. Stob ◽  
...  

2009 ◽  
Vol 21 (1) ◽  
pp. 238 ◽  
Author(s):  
E. Monaco ◽  
A. Lima ◽  
S. Wilson ◽  
S. Lane ◽  
M. Bionaz ◽  
...  

The quantity and accessibility of subcutaneous adipose tissue in humans make it an attractive alternative to bone marrow as a source of adult stem cells for therapeutic purposes. However, before such a cell source substitution can be proposed, the properties of stem cells derived from adipose tissue (ADSC) and bone marrow (BMSC), and their differentiated progeny must be compared in an animal model, such as swine, that adequately simulates the structure and physiology of humans. The objective of this work was to induce adult porcine stem cells isolated from subcutaneous adipose tissue and bone marrow to differentiate in vitro along the adipogenic lineage and to compare their transcript profile properties. ADSC and BMSC were isolated from subcutaneous adipose tissue and femurs of adult pigs, respectively, and differentiated along the adipogenic lineage using specific inducing medium. Cells were incubated up to 4 weeks with medium replaced every 3 days. Histological staining with Oil Red O was performed at 0, 2, 4, 7, 14, 21, 28 days of differentiation (dd) to confirm the adipogenic differentiation. RNA was also extracted at these time points. qPCR was performed on PPARG, DBI, ACSL1, CD36, CEBPA, DGAT2, ADFP, ADIPOQ, SCD. The geometrical mean of GTF2H3, NUBP, and PPP2CB was used as an internal control. Gene expression was analyzed using a mixed model of SAS with repeated time. The adipogenic differentiation of both ADSC and BMSC was confirmed by the Oil Red O positive staining. The relative mRNA abundance of all the genes at dd0 was similar between the ADSC and BMSC. The relative mRNA abundance of most of the genes was also similar between ADSC and BMSC throughout the adipogenic differentiation. ACSL1 and ADIPOQ had analogous expression patterns among the cell types. ACSL1 had relatively large mRNA abundance before differentiation, but ADIPOQ was barely detectable. As a consequence of differentiation, ACSL1 increased in relative mRNA abundance about 10-fold, whereas ADIPOQ mRNA increased about 1000-fold. Temporal expression patterns of SCD, DGAT2, and ADFP were similar. The increase in gene expression was >800% for SCD, >500% for ADFP, and >50 000% for DGAT2 after 7dd. ADSC had significantly higher expression of those genes compared to BMSC at 14 and 28dd. Both ADIPOQ and DGAT2 were almost undetectable prior to differentiation. mRNA expression of CD36 and DBI was similar with a significantly larger increase in expression of ADSC compared with BMSC. Relative mRNA abundance of CEBPA and PPARG was also larger in ADSC compared with BMSC; however, BMSC had a remarkable increase in temporal expression of those genes throughout adipogenic differentiation. These results suggest both cell types can differentiate towards the adipogenic lineage but with quantitatively different gene expression patterns. More investigation is needed before the ADSC can be considered a practical alternative source for stem cells in future human clinical applications. This research was supported by the Illinois Regenerative Medicine Institute.


PeerJ ◽  
2016 ◽  
Vol 4 ◽  
pp. e1768 ◽  
Author(s):  
Jie Zhang ◽  
Jideng Ma ◽  
Keren Long ◽  
Long Jin ◽  
Yihui Liu ◽  
...  

A better understanding of the control of lipogenesis is of critical importance for both human and animal physiology. This requires a better knowledge of the changes of gene expression during the process of adipose tissue development. Thus, the objective of the current study was to determine the effects of development on subcutaneous adipose tissue gene expression in growing and adult pigs. Here, we present a comprehensive investigation of mRNA transcriptomes in porcine subcutaneous adipose tissue across four developmental stages using digital gene expression profiling. We identified 3,274 differential expressed genes associated with oxidative stress, immune processes, apoptosis, energy metabolism, insulin stimulus, cell cycle, angiogenesis and translation. A set of universally abundant genes (ATP8,COX2,COX3,ND1, ND2,SCDandTUBA1B) was found across all four developmental stages. This set of genes may play important roles in lipogenesis and development. We also identified development-related gene expression patterns that are linked to the different adipose phenotypes. We showed that genes enriched in significantly up-regulated profiles were associated with phosphorylation and angiogenesis. In contrast, genes enriched in significantly down-regulated profiles were related to cell cycle and cytoskeleton organization, suggesting an important role for these biological processes in adipose growth and development. These results provide a resource for studying adipose development and promote the pig as a model organism for researching the development of human obesity, as well as being used in the pig industry.


Author(s):  
И.А. Побожева ◽  
А.А. Пантелеева ◽  
Н.Д. Разгильдина ◽  
Е.А. Полякова ◽  
К.В. Драчева ◽  
...  

Дисбаланс в секреции адипокинов жировой тканью при ожирении может играть роль в развитии сердечно-сосудистых заболеваний. Нами было проведено исследование уровня экспрессии генов адипонектина и оментина-1 в жировой ткани у лиц с ожирением и ишемической болезнью сердца (ИБС). Показано, что сниженные концентрация в сыворотке крови и экспрессия гена адипонектина в подкожной жировой ткани могут вносить вклад в развитие ИБС при ожирении. ИБС ассоциирована с низкой концентрация оментина-1 в сыворотке крови. Imbalance in the secretion of adipose tissue adipokines may play a role in the development of cardiovascular diseases associated with obesity. Investigation of adiponectin and omentin-1 genes expression levels in adipose tissue was conducted in patients with obesity and coronary artery disease (CAD). Our study has shown that reduced adiponectin serum concentration and subcutaneous adipose tissue gene expression may contribute to CAD development. CAD is associated with a low serum omentin-1 concentration.


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