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| Status |
Public on Aug 24, 2021 |
| Title |
mouse 3T3L1 adipocytes transduced with Lmo3- or LacZ-Adenovirus |
| Organism |
Mus musculus |
| Experiment type |
Expression profiling by high throughput sequencing
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| Summary |
Background. Obesity and body fat distribution are important risk factors for the development of type 2 diabetes and metabolic syndrome. Evidence has accumulated that this risk is related to intrinsic differences in behavior of adipocytes in different fat depots. LIM Domain Only 3 (LMO3) plays a crucial role in adipogenesis modulating the key adipogenic master switch PPARĪ³ in human, but not mouse, visceral adipose progenitors; however, despite high expression in mature adipocytes, its function in these cells is currently unknown. Aims/Hypothesis. The aim of this study was to determine the potential involvement of LMO3-dependent pathways in the modulation of key functions of mature adipocytes during obesity. Methods. Based on a recently engineered hybrid rAAV serotype Rec2 shown to efficiently transduce both brown adipose tissue (BAT) and white adipose tissue (WAT), we delivered YFP or Lmo3 to epididymal WAT (eWAT) of C57Bl6/J mice on a high fat diet (HFD). The effects of eWAT transduction on metabolic parameters were evaluated 10 weeks later. To further define the role of LMO3 in insulin-stimulated glucose uptake, insulin signaling, adipocyte bioenergetics as well as endocrine function, experiments were conducted in 3T3-L1 adipocytes and newly differentiated human primary mature adipocytes, engineered for transient gain- or loss of LMO3 expression, respectively.Results. AAV transduction of eWAT results in strong and stable Lmo3 expression specifically in the adipocyte fraction over a course of 10 weeks with HFD feeding. Lmo3 expression in eWAT significantly improved glucose clearance and insulin sensitivity in diet-induced obesity, paralleled by increased serum adiponectin. In vitro, Lmo3 expression in 3T3-L1 adipocytes increased insulin-stimulated GLUT4 translocation and glucose uptake as well as mitochondrial oxidative capacity in addition to fatty acid oxidation. On a molecular level, LMO3 augmented PPARg activity, oxidative mitochondrial gene expression, which depended on and the expression of the PPARg co-activator Ncoa1, which was required for LMO3 effects on mitochondria and glucose uptake. In human mature adipocytes, LMO3 overexpression promoted, while silencing of LMO3 suppressed mitochondrial oxidative capacity. Conclusions. LMO3 expression in visceral adipose tissue regulates multiple genes that preserve adipose tissue functionality during obesity, such as glucose tolerance, insulin sensitivity and adiponectin secretion. Together with increased PPARĪ³ activity, these gene expression changes promote insulin-induced GLUT4 translocation, glucose uptake in addition to increased mitochondrial oxidative capacity, limiting HFD-induced adipose dysfunction. These data add LMO3 as a novel regulator improving visceral adipose tissue function during obesity.
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| Overall design |
De-novo differentiated mature 3T3-L1 adipocytes were transduced with control (LacZ) or Lmo3 overexpressing Adenovirus; RNA was isolated 72 hrs after transduction and subjected to RNA-Seq analysis. RNA was harvested from three separate adenoviral infections per genotype (LacZ and Lmo3, respectively)
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| Contributor(s) |
Bilban M, Jeitler M, Derdak S |
| Citation(s) |
34018016 |
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| Submission date |
Aug 06, 2020 |
| Last update date |
Aug 25, 2021 |
| Contact name |
Markus Jeitler |
| E-mail(s) |
markus.jeitler@meduniwien.ac.at
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| Organization name |
Medical University Vienna
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| Street address |
Lazarettgasse 14
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| City |
Vienna |
| ZIP/Postal code |
A-1090 |
| Country |
Austria |
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| Platforms (1) |
| GPL19057 |
Illumina NextSeq 500 (Mus musculus) |
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| Samples (6)
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| This SubSeries is part of SuperSeries: |
| GSE139163 |
LMO3 reprogramms viseral adipocyte metabolism during obesity |
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| Relations |
| BioProject |
PRJNA655613 |
| SRA |
SRP276346 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE155781_RAW.tar |
770.0 Kb |
(http)(custom) |
TAR (of TXT) |
SRA Run Selector |
| Raw data are available in SRA |
| Processed data provided as supplementary file |
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