|
| Status |
Public on Aug 24, 2021 |
| Title |
LMO3 reprogramms viseral adipocyte metabolism during obesity [Human] |
| Organism |
Homo sapiens |
| Experiment type |
Expression profiling by array
|
| Summary |
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. On a molecular level, LMO3 expression in eWAT increased pathways indicative of adipogenesis and PPARg signaling as well as mitochondrial activity, paralleled by a suppression of adipose tissue fibrosis. 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. LMO3 overexpression promoted, while silencing of LMO3 suppressed, mitochondrial oxidative capacity in human mature adipocytes. 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 PPARγ 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.
|
| |
|
| Overall design |
Treated Human mature adipocytes, de-novo differentiated from stromal vascular fraction (SVF) derived from lipoaspirates from 2 different donors. One pool of adipocytes was transfected with a non-targeting siRNA (siCtrl) and the other pool was transfected with a siRNA targeting human LMO3 gene.
|
| |
|
| Contributor(s) |
Bilban M, Jeitler M |
| Citation(s) |
34018016 |
| |
| Submission date |
Oct 21, 2019 |
| Last update date |
Aug 25, 2021 |
| Contact name |
Markus Jeitler |
| E-mail(s) |
markus.jeitler@meduniwien.ac.at
|
| Organization name |
Medical University Vienna
|
| Street address |
Lazarettgasse 14
|
| City |
Vienna |
| ZIP/Postal code |
A-1090 |
| Country |
Austria |
| |
|
| Platforms (1) |
| GPL6244 |
[HuGene-1_0-st] Affymetrix Human Gene 1.0 ST Array [transcript (gene) version] |
|
| Samples (4)
|
|
| This SubSeries is part of SuperSeries: |
| GSE139163 |
LMO3 reprogramms viseral adipocyte metabolism during obesity |
|
| Relations |
| BioProject |
PRJNA578664 |
Less...
More...