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| Status |
Public on Jul 06, 2006 |
| Title |
Complementary action of the PGC-1 coactivators in mitochondrial biogenesis and brown fat differentiation |
| Organism |
Mus musculus |
| Experiment type |
Expression profiling by array
|
| Summary |
Mitochondria play an essential role in the ability of brown fat to generate heat, and the PGC-1 coactivators control several aspects of mitochondrial biogenesis. To investigate their specific roles in brown fat cells, we generated immortal preadipocyte lines from the brown adipose tissue of mice lacking PGC-1α. We could then efficiently knockdown PGC-1β expression by shRNA expression. Loss of PGC-1α did not alter brown fat differentiation but severely reduced the induction of thermogenic genes. Cells deficient in either PGC-1α or PGC-1β coactivators showed a small decrease in the differentiation-dependant program of mitochondrial biogenesis and respiration; however, this increase in mitochondrial number and function was totally abolished during brown fat differentiation when both PGC-1α and PGC-1β were deficient. These data show that PGC-1α is essential for brown fat thermogenesis but not brown fat differentiation, and the PGC-1 coactivators play an absolutely essential but complementary function in differentiation-induced mitochondrial biogenesis. Affymetrix microarray analysis of total RNA from wt, PGC-1α KO and PGC-1α KO
cells expressing an RNAi specific for PGC-1β knockdown was performed. Of the 461
mitochondrial genes analyzed, 181 were found to be at least 20% different between wt
and defective PGC-1α and β adipocytes (p < 0.05). More than 85% of these genes were downregulated in cells deficient for PGC-1alpha and PGC-1beta.
Keywords: Analysis of mitochondrial gene expression
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| Overall design |
Brown preadipocytes that were either WT, KO for PGC-1alpha, or KO for PGC-1alpha and deficient for PGC-1beta (knockdown through siRNA expression) were differentiated for seven days. RNA was made from biological replicates of the three different types of brown adipocytes (WT, KO expressing a control siRNA, KO expressing a siRNA specific for PGC-1beta knockdown).
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| Contributor(s) |
Uldry M, Yang W, St-Pierre J, Lin J, Seale P, Spiegelman BM |
| Citation(s) |
16679291 |
| |
| Submission date |
Jun 09, 2006 |
| Last update date |
Feb 11, 2019 |
| Contact name |
Marc Uldry |
| E-mail(s) |
marc_uldry@dfci.harvard.edu
|
| Phone |
6176324661
|
| Organization name |
Dana Farber Cancer Institute
|
| Street address |
1 Jimmy Fund Way
|
| City |
Boston |
| State/province |
MA |
| ZIP/Postal code |
02139 |
| Country |
USA |
| |
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| Platforms (1) |
| GPL1261 |
[Mouse430_2] Affymetrix Mouse Genome 430 2.0 Array |
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| Samples (6)
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| GSM113409 |
WT differentiated brown fat cells (rep1) |
| GSM113411 |
WT differentiated brown fat cells (rep2) |
| GSM113461 |
PGC-1alpha -/- differentiated brown fat cells expressing a control siRNA (rep1) |
| GSM113462 |
PGC-1alpha -/- differentiated brown fat cells expressing a control siRNA (rep2) |
| GSM113463 |
PGC-1alpha -/- differentiated brown fat cells expressing a siRNA specific for PGC-1beta knockdown (rep1) |
| GSM113464 |
PGC-1alpha -/- differentiated brown fat cells expressing a siRNA specific for PGC-1beta knockdown (rep2) |
|
| Relations |
| BioProject |
PRJNA96677 |
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