NOTCH Receptors and DLK Proteins Enhance Brown Adipogenesis in Mesenchymal C3H10T1/2 Cells
Abstract
:1. Introduction
2. Materials and Methods
2.1. Plasmids, Cell Culture, and Transfections
2.2. Quantitative PCR and RT-PCR mRNA Transcription Analysis
2.3. Culture Supernatants and Conditioned Media
2.4. Protein Sample Preparation and Western Blotting
2.5. Luciferase Assays
2.6. Adipogenic Assays and Mitochondrial Biogenesis Analysis
2.7. Lipolytic Potential, Lactate Release to the Extracellular Medium, and Oxygen Consumption Rate (OCR) Assays
2.8. Statistical Analysis
3. Results
3.1. Comparison of Adipogenesis Levels and Expression Levels of Some of the Notch Family Genes between Multipotent C3H10T1/2 Cells and 3T3-L1 Preadipocytes
3.2. Analysis of the Expression of NOTCH Receptors and DLK Proteins in Multipotent C3H10T1/2 Cells
3.3. Overexpression of NOTCH Receptors or DLK Proteins Enhances the Adipogenic Potential of Multipotent C3H10T1/2 Cells
3.4. Overexpression of NOTCH3 Receptor or DLK Proteins Enhances the Brown Adipogenesis of Multipotent C3H10T1/2 Cells
4. Discussion
5. Conclusions
- C3H10T1/2 mesenchymal cells display lower DLK expression levels and higher NOTCH expression, activity, and signaling levels than 3T3-L1 preadipocytes.
- There are complex feedback regulation loops among Notch and Dlk genes in C3H10T1/2 cells.
- Even though Notch1 gene expression is upregulated at the end of the adipogenic process, the expression of the rest of Notch genes and NOTCH receptors’ target genes Hes1 and Hey1 is downregulated.
- The overexpression of each of the four NOTCH receptors, except for NOTCH4, enhances the adipogenic levels of multipotent C3H10T1/2 cells.
- NOTCH activation levels can modulate the adipocyte fate of multipotent C3H10T1/2 cells.
- The overexpression of NOTCH3 receptor or DLK proteins determine a brown adipogenesis fate in multipotent C3H10T1/2 adipocytes.
Supplementary Materials
Author Contributions
Funding
Acknowledgments
Conflicts of Interest
Abbreviations
aP2 | adipocyte protein 2/fatty acid binding protein 4. |
APOB | apoliprotein B. |
BAT | brown adipose tissue. |
CEBPβ | CCAAT Enhancer Binding Protein Beta. |
CIDEA | cell death-inducing DNA fragmentation factor, alpha subunit-like effector A. |
CM | conditioned medium. |
CSL/RBPJκ | CBF1, Suppressor of Hairless, Lag-1/recombination signal binding protein for immunoglobulin kappa J region. |
CT | cycle threshold. |
DAPT | N-[N-(3, 5-Difluorophenacetyl)-L-alanyl]-S-phenylglycine t-butyl ester. |
DLK1 | DELTA-like 1 homolog. |
DLK2 | DELTA-like 2 homolog. |
DLK | DELTA-like homolog. |
DLL4 | DELTA-Like Canonical NOTCH Ligand 4. |
DNER | DELTA/NOTCH EGF-like Repeat Containing. |
DOS | DELTA and OSM-11 domain. |
DSL | DELTA-SERRATE-LAG-2. |
E | oligonucleotide efficiency. |
ECAR | extracellular acidification rate. |
EGFL7 | Epidermal growth factor-like protein 7. |
GYK | glycerol kinase. |
HA | influenza hemagglutinin. |
HES1 | hairy and enhancer of split 1. |
HEY1 | hairy and enhancer-of-split related with YRPW motif 1. |
IBMX | 3-Isobutyl-1-methylxanthine. |
JAG1 | JAGGED canonical NOTCH ligand 1. |
LP | lipolytic potential. |
MSCs | mesenchymal stem cells. |
mtCYTB | mitochondrial cytochrome b. |
NICD | intracellular active domain of NOTCH receptors. |
OCR | oxygen consumption rate. |
P0 | ribosomal protein P0 |
PGC1α | peroxisome proliferator activated receptor gamma coactivator 1-alpha. |
PPARγ | peroxisome proliferator activated receptor gamma. |
PRDM16 | PR domain-containing 16. |
qPCR/qRT-PCR | quantitative-polymerase chain reaction/quantitative reverse transcription-polymerase chain reaction. |
SIRT1 | Sirtuin 1. |
TACE | ADAM metallopeptidase domain 17. |
UCP1 | mitochondrial uncoupling protein 1. |
UCP2 | uncoupling protein 2. |
WAT | white adipose tissue. |
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Protein | Dilution of Primary and Secondary Antibodies | Company |
---|---|---|
NOTCH1 | Rabbit anti-NOTCH1 C20R (1:1000) | Santa Cruz Biotechnology |
NOTCH2 | Goat anti-NOTCH2 M20 (1:500) | Santa Cruz Biotechnology |
NOTCH3 | Rabbit anti-NOTCH3 (1:1000) | Abcam |
NOTCH4 | Rabbit anti-NOTCH4 (1:1000) | Upstate Millipore |
HA | Mouse anti-HA 16B12 (1:5000) | Covance |
DLK1 (DELTA-like 1 homolog) | Rabbit anti-DLK1 (1:1000) | Nueda et al., 2008 |
DLK2 (DELTA-like 2 homolog) | Rabbit polyclonal anti-mouse DLK2-C-terminal (1:500) | Abcam |
α-Tubulin | Mouse anti-alpha-Tubulin (1:5000) | Sigma |
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Rodríguez-Cano, M.-M.; González-Gómez, M.-J.; Sánchez-Solana, B.; Monsalve, E.-M.; Díaz-Guerra, M.-J.M.; Laborda, J.; Nueda, M.-L.; Baladrón, V. NOTCH Receptors and DLK Proteins Enhance Brown Adipogenesis in Mesenchymal C3H10T1/2 Cells. Cells 2020, 9, 2032. https://doi.org/10.3390/cells9092032
Rodríguez-Cano M-M, González-Gómez M-J, Sánchez-Solana B, Monsalve E-M, Díaz-Guerra M-JM, Laborda J, Nueda M-L, Baladrón V. NOTCH Receptors and DLK Proteins Enhance Brown Adipogenesis in Mesenchymal C3H10T1/2 Cells. Cells. 2020; 9(9):2032. https://doi.org/10.3390/cells9092032
Chicago/Turabian StyleRodríguez-Cano, María-Milagros, María-Julia González-Gómez, Beatriz Sánchez-Solana, Eva-María Monsalve, María-José M. Díaz-Guerra, Jorge Laborda, María-Luisa Nueda, and Victoriano Baladrón. 2020. "NOTCH Receptors and DLK Proteins Enhance Brown Adipogenesis in Mesenchymal C3H10T1/2 Cells" Cells 9, no. 9: 2032. https://doi.org/10.3390/cells9092032