282 ADIPOGENIC DIFFERENTIATION IN VITRO OF PORCINE ADULT MESENCHYMAL STEM CELLS

2009 ◽  
Vol 21 (1) ◽  
pp. 238 ◽  
Author(s):  
E. Monaco ◽  
A. Lima ◽  
S. Wilson ◽  
S. Lane ◽  
M. Bionaz ◽  
...  
Keyword(s):  
Gene Expression ◽  
Stem Cells ◽  
Bone Marrow ◽  
Adipose Tissue ◽  
Subcutaneous Adipose Tissue ◽  
Adipogenic Differentiation ◽  
Expression Patterns ◽  
Mrna Abundance ◽  
Subcutaneous Adipose

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.

286 OSTEOGENIC DIFFERENTIATION IN VITRO OF PORCINE ADULT MESENCHYMAL STEM CELLS

2008 ◽  
Vol 20 (1) ◽  
pp. 223
Author(s):  
A. Lima ◽  
E. Monaco ◽  
S. Wilson ◽  
D. Kim ◽  
C. Feltrin ◽  
...  
Keyword(s):  
Stem Cells ◽  
Bone Marrow ◽  
Alkaline Phosphatase ◽  
Adipose Tissue ◽  
Osteogenic Differentiation ◽  
Subcutaneous Adipose Tissue ◽  
Cell Types ◽  
Alizarin Red ◽  
Subcutaneous Adipose

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 (ADSCs) and bone marrow (MSCs) and their differentiated progeny must be compared in an animal model 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 osteoblastic lineage and to compare their morphological, phenotypic, and genotypic properties. MSCs and ADSCs were isolated respectively from femurs and subcutaneous adipose tissue of adult pigs and cultured in vitro using DMEM supplemented with 10% fetal bovine serum (FBS), 1% penicillin G-streptomycin, and 5.6 mg L–1 amphotericin B. After 3 passages, cells were differentiated along the osteogenic lineage using lineage-specific inducing medium. Osteogenic medium contained 100 nm dexamethasone, 10 mm β-glycerophosphate, and 0.005 mm ascorbic acid-2-phosphate. Osteogenic cultures were incubated for 4 weeks in 95% air and 5% CO2 at 39�C. Spent medium was replaced with fresh medium every 3 days. Histological staining with alkaline phosphatase, Von Kossa, and alizarin red S were performed at 0, 2, 4, 7, 14, 21, and 28 days of differentiation (dd). At the same time points, RNA was extracted. qPCR was performed on COL1A1, BGLAP, SPARC, and SPP1. As internal control, the geometrical mean of GTF2H, NUBP, and PPP2C was used. Relative mRNA abundance between cell types was calculated using 1/efficiencydCT. The osteogenic differentiation of both MSCs and ADScs was confirmed by the organization of the cells in nodules and by alkaline phosphatase-, Von Kossa-, and alizarin red S-positive staining. The percent relative abundance of the 4 genes in both cell types was COL1A1 (ca. 50) > SPARC (ca. 45) > SPP1 (ca. 5) > BGLAP ( < 0.1). Cell types showed similar mRNA abundance for COL1A1 and SPARC while SPP1 and BGLAP were, respectively, 10- and 19-fold higher in MSCs than in ADSCs. All of the genes had the same pattern among tissues during differentiation except for SPP1, which showed a >10-fold increase at 14 v. 0 dd only for MSCs. Adipose-derived stem cells demonstrated a clear osteogenic differentiation and similar expression and pattern of the two osteogenic genes most abundant in MSCs (COL1A1 and SPARC). However, the higher abundance of SPP1 and BGLAP and the different behavior of SPP1 in MSCs suggest a different transcription profile between the two cell types. From these preliminary results, adipose tissue can be a practical alternative source for stem cells in future human clinical applications.

scholarly journals Differentiation of mesenchymal stem cells derived from human bone marrow and subcutaneous adipose tissue into pancreatic islet-like clusters in vitro

2013 ◽  
Vol 18 (1) ◽  
Author(s):  
Dhanasekaran Marappagounder ◽  
Indumathi Somasundaram ◽  
Sudarsanam Dorairaj ◽  
Rajkumar Sankaran
Keyword(s):  
Stem Cells ◽  
Bone Marrow ◽  
Mesenchymal Stem Cells ◽  
Adipose Tissue ◽  
Pancreatic Islet ◽  
Subcutaneous Adipose Tissue ◽  
Lineage Differentiation ◽  
Wide Range ◽  
Subcutaneous Adipose

AbstractAlthough stem cells are present in various adult tissues and body fluids, bone marrow has been the most popular source of stem cells for treatment of a wide range of diseases. Recent results for stem cells from adipose tissue have put it in a position to compete for being the leading therapeutic source. The major advantage of these stem cells over their counterparts is their amazing proliferative and differentiation potency. However, their pancreatic lineage transdifferentiation competence was not compared to that for bone marrow-derived stem cells. This study aims to identify an efficient source for transdifferentiation into pancreatic islet-like clusters, which would increase potential application in curative diabetic therapy. The results reveal that mesenchymal stem cells (MSC) derived from bone marrow and subcutaneous adipose tissue can differentiate into pancreatic islet-like clusters, as evidenced by their islet-like morphology, positive dithizone staining and expression of genes such as Nestin, PDX1, Isl 1, Ngn 3, Pax 4 and Insulin. The pancreatic lineage differentiation was further corroborated by positive results in the glucose challenge assay. However, the results indicate that bone marrow-derived MSCs are superior to those from subcutaneous adipose tissue in terms of differentiation into pancreatic islet-like clusters. In conclusion, bone marrow-derived MSC might serve as a better alternative in the treatment of diabetes mellitus than those from adipose tissue.

Influence of somatotropin on lipid metabolism and IGF gene expression in porcine adipose tissue

1992 ◽  
Vol 263 (4) ◽  
pp. E637-E645 ◽  
Author(s):  
C. K. Wolverton ◽  
M. J. Azain ◽  
J. Y. Duffy ◽  
M. E. White ◽  
T. G. Ramsay
Keyword(s):  
Gene Expression ◽  
Adipose Tissue ◽  
Dietary Fat ◽  
Subcutaneous Adipose Tissue ◽  
Proliferation And Differentiation ◽  
Igf I ◽  
Systemic Factors ◽  
Subcutaneous Adipose ◽  
Acid Esterification

The present study was designed to evaluate the effects of porcine somatotropin (pST) treatment (2 mg/day) and dietary fat (10%) separately and in combination on the metabolic activity of subcutaneous adipose tissue, serum adipogenic activity, and insulin-like growth factor (IGF) gene expression within adipose tissue from growing 5- to 6-mo-old barrows. This study attempted to determine how these factors might contribute to the reported changes in adiposity of treated swine. Biopsies of adipose tissue were collected after 28 days of treatment following anesthesia with thiopental sodium (15 mg/kg iv). Somatotropin inhibited in vitro glucose oxidation and lipogenesis in adipose tissue but did not affect fatty acid esterification. Adipogenic activity of serum was not altered by pST treatment. Subcutaneous adipose tissue contained mRNA for IGF-I and -II, and pST administration increased the abundance of IGF-I mRNA. Dietary fat had no effect on these variables. Thus somatotropin reduces glucose metabolism in porcine subcutaneous adipose tissue. Preadipocyte proliferation and differentiation are not affected by somatotropin through its actions on systemic factors. Dietary fat provides no additional benefit in combination with pST administration to affect accretion of adipose tissue in growing swine.

scholarly journals Bone marrow- and subcutaneous adipose tissue-derived mesenchymal stem cells: Differences and similarities

Cell Cycle ◽  
2012 ◽  
Vol 11 (2) ◽  
pp. 377-383 ◽  
Author(s):  
Renata I. Dmitrieva ◽  
Izida R. Minullina ◽  
Anna A. Bilibina ◽  
Olga V. Tarasova ◽  
Sergey V. Anisimov ◽  
...  
Keyword(s):  
Stem Cells ◽  
Bone Marrow ◽  
Mesenchymal Stem Cells ◽  
Adipose Tissue ◽  
Subcutaneous Adipose Tissue ◽  
Subcutaneous Adipose

scholarly journals Knockdown of CDC20 Promotes Adipogenesis of Bone Marrow-derived Stem Cells

2021 ◽  
Author(s):  
Yangge Du ◽  
Yunsong Liu ◽  
Yongsheng Zhou ◽  
Ping Zhang
Keyword(s):  
Stem Cells ◽  
Bone Marrow ◽  
Adipose Tissue ◽  
Western Blot ◽  
Adipogenic Differentiation ◽  
Conditional Knockout ◽  
Qrt Pcr ◽  
Oil Red O Staining ◽  
Oil Red O

Abstract Background: Bone is a rigid organ that provides support and physical protection to vital organs of the body. Several bone loss disorders are commonly associated with increased bone marrow adipose tissue. Bone marrow mesenchymal stromal/stem cells (BMSCs) are multipotent progenitors differentiating into osteoblasts, adipocytes, and chondrocytes. CDC20 is a co-activator of APC/C, required for full ubiquitin ligase activity. In our previous study, CDC20 promoted the osteogenic commitment of BMSCs and Cdc20 conditional knockout mice suggested a decline in bone mass. In this study, we investigated the function of CDC20 in the adipogenic differentiation of BMSCs and provided a new clue between adipogenesis and osteogenesis. Methods: Lentivirus containing CDC20 shRNA was used for CDC20 knockdown in hBMSCs. Primary mBMSCs were isolated from Cdc20f/f and Sp7-Cre;Cdc20f/f mice. Adipogenesis was examined by qRT-PCR and western blot analysis of adipogenic regulators, Oil Red O staining and transplantation into nude mice. The CDC20 knockout efficiency was determined through immunochemistry, qRT-PCR and western blot of bone marrow. Accumulation of adiposity was measured through histology and staining of bone sections. Results: CDC20 expression in hBMSCs was significantly decreased during adipogenic differentiation. Knockdown of CDC20 enhanced adipogenic differentiation of hBMSCs in vitro. CDC20-knockdown hBMSCs showed more adipose tissue–like constructs in H&E staining and Oil Red O staining. Sp7-Cre;Cdc20f/f mice presented increased adipocytes in bone marrow compared with control mice. mBMSCs from Sp7-Cre;Cdc20f/f mice exerted upregulated adipogenic differentiation. Conclusions: Our findings showed that knockdown of CDC20 enhanced adipogenesis of h(m)BMSCs in vitro and in vivo. Overall, CDC20 regulated both adipogenesis and osteogenesis of BMSCs, and may lead to the development of new therapeutic target for “fatty bone” and osteoporosis.

scholarly journals Dynamic gene expression profiles during postnatal development of porcine subcutaneous adipose

PeerJ ◽  
2016 ◽  
Vol 4 ◽  
pp. e1768 ◽  
Author(s):  
Jie Zhang ◽  
Jideng Ma ◽  
Keren Long ◽  
Long Jin ◽  
Yihui Liu ◽  
...  
Keyword(s):  
Gene Expression ◽  
Cell Cycle ◽  
Adipose Tissue ◽  
Subcutaneous Adipose Tissue ◽  
Developmental Stages ◽  
Expression Profiles ◽  
Expression Patterns ◽  
Model Organism ◽  
Digital Gene Expression ◽  
Subcutaneous Adipose

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.

401 MIGRATION AND THERAPEUTIC POTENTIAL OF PORCINE ADULT ADIPOSE-DERIVED MESENCHYMAL STEM CELLS

2010 ◽  
Vol 22 (1) ◽  
pp. 357 ◽  
Author(s):  
S. M. Wilson ◽  
E. Monaco ◽  
M. S. Goldwasser ◽  
S. G. Clark ◽  
W. L. Hurley ◽  
...  
Keyword(s):  
Stem Cells ◽  
Adipose Tissue ◽  
Subcutaneous Adipose Tissue ◽  
Adult Stem Cells ◽  
Bone Defects ◽  
Adipose Derived Stem Cells ◽  
Subcutaneous Adipose ◽  
Time Point

Bone marrow is one current source of adult stem cells for therapeutic purposes; however, the magnitude and accessibility of subcutaneous adipose tissue in humans make it an attractive alternative. Numerous in vitro studies have been conducted to determine how these cells act in vitro, but it is imperative to determine the vast abilities of these cells in vivo. The objective of this study was to evaluate in vivo migration and bone healing ability after transplanting adipose-derived stem cells (ADSC) in a swine model. Adipose-derived stem cells were isolated from subcutaneous adipose tissue of adult Yorkshire pigs and cultured in vitro. At 80 to 90% confluence/passage 3, the cells were trypsinized and labeled in suspension with carboxyfluorescein succinimidyl ester (CFDA-SE). This project included 20 pigs weighing between 63.5 and 81.7 kg. Bilateral mandibular osteoectomies with 10-mm defects were performed on each pig. Of the 20 pigs, half received a treatment of 2.5 million CFDA-SE labeled stem cells administered directly into each defect (DI), and the remaining half received a treatment of approximately 5 million CFDA-SE labeled stem cells through an ear vein injection via catheter (EVI). The time points were 1 h and 2 and 4 wk, with 2 pigs per time with the DI and EVI treatments. Pigs were slaughtered at each time, and spleen, liver, lung, kidney, ear vein, blood, and mandible tissues were collected. Blood samples were collected from the jugular vein with EDTA and processed via flow cytometry after collection. Tissues were fixed in 10% buffered formalin for histology. Fluorescent microscopy (CFDA-SE excitation/emission is 492/517 nm) has confirmed that transplanted ADSC do indeed migrate to a site of injury or trauma. Labeled cells were also present in blood collected from the 1-h time point group. Currently, we have not seen the presence of labeled ADSC in the other tissues (spleen, liver, lung, and kidney) after the 1-h time point. We did observe that ADSC administered by DI and EVI were able to significantly heal and regenerate bone defects within 4 wk post-surgery (P < 0.05, ANOVA with F-test), in contrast to bone defects in pigs that did not receive cell injections (control). Evidence of ADSC-related healing and bone regeneration was evident by gross visualization, dual-energy x-ray absorptiometry (DXA) and micro computer tomography (microCT) analysis. The clinical implications of these results are significant for treating many diseases in which inflammation or defects exist, such as cardiac disease, neurological disease, or traumatic injuries to both soft and hard tissue. If the adult stem cells can be harvested from fat, encouraged to produce bone or cartilage, and then reinserted into defects, treatment protocols for trauma victims could be developed that would reduce the need for alternate harvesting techniques for bone. This work was support by a grant from the Illinois Regenerative Medicine Institute (IDPH # 63080017).

390 ISOLATION AND ADIPOGENESIS OF GRIZZLY BEAR MESENCHYMAL STEM CELLS

2010 ◽  
Vol 22 (1) ◽  
pp. 351
Author(s):  
A. J. Maki ◽  
I. Omelogu ◽  
E. Monaco ◽  
M. E. McGee-Lawrence ◽  
R. M. Bradford ◽  
...  
Keyword(s):  
Stem Cells ◽  
Bone Marrow ◽  
Mesenchymal Stem Cells ◽  
Adipose Tissue ◽  
Stem Cell ◽  
In Vitro Model ◽  
Adipogenic Differentiation ◽  
Grizzly Bear ◽  
Vitro Model

During winter hibernation, grizzly bears (Ursus arctos horribilis) do not eat but instead rely on internal fat stores as a primary source of metabolic energy. The resulting seasonal fluctuations in appetite and body mass make the grizzly bear a naturally occurring animal model for human conditions such as obesity and anorexia. An in vitro model of hibernating bear stem cells might enhance our understanding of processes such as stem cell proliferation and differentiation. Mesenchymal stem cells, derived from bone marrow and adipose tissue among others, differentiate into adipocytes and might play important roles in energy metabolism. In the current study, we examined the in vitro viability and morphology of mesenchymal stem cells isolated from grizzly bear adipose tissue (ADSC) and bone marrow (BMSC); these ADSC and BMSCs underwent adipogenic differentiation for 0, 7, 14, 21, and 28 days. Bone marrow stem cells and ADSC were isolated using mechanical disaggregation, collagenase digestion, centrifugation, and plating onto tissue culture polystyrene. Cell viability and proliferation was quantified using the colony forming unit assay and a hemocytometer. Both stem cell types were differentiated into adipocytes using 10 μM insulin, 1 μM dexamethasone, and 0.5 mM isobutylmethylxanthine (all Sigma- Aldrich, St. Louis, MO, USA) with the addition of 10% fetal bovine (FBS) or bear serum from the active feeding period. Adipogenic differentiation was confirmed using Oil Red O and quantified using ImageJ. Statistical analysis was performed using an unpaired t-test between treatments of the same time point. All cells were isolated within 28 h of tissue harvest. Adipose-derived stem cells formed an average of 11 colonies (0.011%), whereas BMSC formed 1.5 colonies (0.0015%) per 100 000 cells. Doubling time forADSC was approximately 54 h in 10% FBS. BothADSC and BMSC had an initial spindle-shaped morphology, which gradually became more rounded during adipogenic differentiation. For bear serum at Day 28, ADSC had a significantly (P < 0.01) greater stained area per cell than did BMSC. In summary, both types of mesenchymal stem cells successfully differentiated into adipocytes and maintained viability. In conclusion, grizzly bear mesenchymal stem cells canbesuccessfully isolated, expanded, and differentiated in culture. These results allow for future studies using the bear as an in vitro model for fat metabolism during hibernation and active periods. This work was partially supported by the Carle Foundation Hospital, the Intel Scholar’s Research Program, USDA Multi-State Research Project W1171, and the Illinois Regenerative Medicine Institute (IDPH # 63080017). In addition, the authors would like to thank Agatha Luszpak for support with the analysis.

scholarly journals Expression of the CD11c gene in subcutaneous adipose tissue is associated with cytokine level and insulin resistance in women with polycystic ovary syndrome

2012 ◽  
Vol 167 (5) ◽  
pp. 705-713 ◽  
Author(s):  
Tao Tao ◽  
Shengxian Li ◽  
Aimin Zhao ◽  
Yanyun Zhang ◽  
Wei Liu
Keyword(s):  
Gene Expression ◽  
Insulin Resistance ◽  
Adipose Tissue ◽  
Polycystic Ovary Syndrome ◽  
Subcutaneous Adipose Tissue ◽  
Polycystic Ovary ◽  
Mrna Abundance ◽  
Model Assessment ◽  
Ovary Syndrome ◽  
Subcutaneous Adipose

Objective Alterations in the phenotypes of macrophages in adipose tissue play a key role in inflammation and insulin resistance (IR). The phenotypes of macrophages in subcutaneous adipose tissue (SAT) and the relationship between proinflammation markers and IR in women with polycystic ovary syndrome (PCOS) remain unclear. The objectives of this study are to characterize the gene expression of macrophage markers and cytokines in the SAT of PCOS women and to estimate their relationships with circulating levels of cytokines and IR. Methods The cross-sectional study involves 16 PCOS women and 18 normal control women. Cytokines and macrophage markers in the circulation and SAT were determined using ELISA, quantitative PCR, or immunofluorescence staining. IR was estimated using the homeostasis model assessment (HOMA-IR). Results The gene expression levels of CD11c along with TNF α and leptin in SAT remained significantly higher in PCOS women than in normal women (P<0.05). However, no significant differences were found in CD68 mRNA expression in SAT between women with and without PCOS (P>0.05). Furthermore, CD11c mRNA abundance provided a stronger contribution to models predicting serum levels of TNFα (sTNFα) than did CD68 mRNA abundance. Lastly, increased sTNFα was associated with increased HOMA-IR in PCOS women, and this association was independent of both overall and visceral adiposity. Conclusion The high expression level of CD11c mRNA in SAT was proved to be an important feature in PCOS women. Furthermore, CD11c mRNA abundance made a stronger contribution to models predicting sTNFα in which existing proinflammatory properties might significantly contribute to the pathogenesis of IR in PCOS women.

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 ◽  
...  
Keyword(s):  
Gene Expression ◽  
Clinical Trial ◽  
Adipose Tissue ◽  
Randomized Clinical Trial ◽  
Subcutaneous Adipose Tissue ◽  
Expression Patterns ◽  
Expression Change ◽  
Adipose Tissue Gene Expression ◽  
Subcutaneous Adipose ◽  
Tissue Gene Expression

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.)

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