Estudi de la funció del coactivador transcripcional PGC-1β en el teixit adipós blanc i la seva implicació en el desenvolupament de resistència a insulina
PGC-1β regulates the expression of mitochondrial genes involved in oxidative metabolism in white adipose tissue. Knockout of PGC-1β in adipocytes reduces the expression of genes related to the tricarboxylic acid cycle and oxidative phosphorylation, as well as levels of oxidative enzymes and mitochondrial DNA content. Rosiglitazone treatment increases mitochondrial gene expression and oxidative function in a PGC-1β-dependent manner. However, loss of PGC-1β and mitochondrial oxidative function in adipocytes does not induce whole-body or tissue-specific insulin resistance.
Similar to Estudi de la funció del coactivador transcripcional PGC-1β en el teixit adipós blanc i la seva implicació en el desenvolupament de resistència a insulina
Similar to Estudi de la funció del coactivador transcripcional PGC-1β en el teixit adipós blanc i la seva implicació en el desenvolupament de resistència a insulina (20)
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Estudi de la funció del coactivador transcripcional PGC-1β en el teixit adipós blanc i la seva implicació en el desenvolupament de resistència a insulina
1. Study of the role of the PGC-1β transcriptional coactivator
in white adipose tissue and
its implication in the development of insulin resistance
Natàlia Enguix Elena
Laboratory of Metabolism and Obesity
Unit of Diabetes and Metabolism
4. Decreased mitochondrial mass and function in diabetic patients is associated with
low PGC-1 expression
Control Diabetic
Skeletal Muscle
(Patti et al, PNAS 2003)
Control Diabetic
PGC-1 mRNA Mitochondrial Mass
White Adipose Tissue
(Bogacka et al, Diabetes 2005)
No Diabetic Placebo Pioglitazone No Diabetic Placebo Pioglitazone
Control Control
Diabetic Diabetic
5. Expression of mitochondrial genes and mitochondrial biogenesis is not altered
in WAT of PGC-1-FAT-KO mice
loxP loxP
1 2 3 4 5 6 7 8 9 10 11 12 13 Floxed allele
+ aP2-Cre
1 2 3 6 7 8 9 10 11 12 13 PGC-1-FAT-KO
Gene Expression
1.6 Wildtype
mRNA (a.u.)
1.2 PGC-1-FAT-KO
0.8
0.4 ** **
0
Kidney Liver Testis Spleen Muscle Thymus BAT WAT
Gene Expression mtDNA
White Adipose Tissue
1,5 1,5
mRNA (a.u.)
1 1,0
a.u.
0,5 0,5
0 0,0
wt ko
Pardo et al. PLoS One (2011)
13. Lack of PGC-1β in adipocytes does not induce whole body or tissue-specific insulin
resistance
Glucose Tolerance Test
450 Wt + Vehicle
KO + Vehicle
350
Glucose (mg/dL)
Wt + Rosiglitazone
KO + Rosiglitazone
250
150
50
0 20 40 60 80 100 120
Time (min)
Insulin Tolerance Test
150
Glucose (mg/dL)
100
50
0
0 20 40 60 80 100 120
Time (min)
14. Conclusions
PGC-1β in white adipose tissue specifically regulates the expression of genes
involved in mitochondrial energy production.
PGC-1β but not PGC-1α mediates the rosiglitazone-induced expression of
mitochondrial genes and the oxidative capacity of white adipose tissue.
Full mitochondrial oxidative function is not required for the insulin-sensitizing
effects of thiazolidinediones.