Evidence for the role of AMPK in regulating PGC-1 alpha expression and mitochondrial proteins in mouse epididymal adipose tissue
Funding agencies: This research was supported by a Discovery Grant from the Natural Sciences and Engineering Research Council of Canada to DW and an Operating Grant from the Canadian Institutes of Health Research to GRS. DW and GRS are Tier II Canada Research Chairs. BEK and GRS were supported by grants and fellowships from the Australian Research Council (BEK), the National Health and Medical Research Council (BEK, GRS), and the Victorian Government's Operational Infrastructure Support Program.
Disclosures: Nothing to report. Full financial disclosures and author notes may be found in the online version of this article.
Author Contributions: ZW, GRS, and DW designed the experiments. ZW, LC, and JRM performed the experiments. ZW, LC, JRM, and DW analyzed the data. BEK was involved in generating the knockout mice. ZW and DW wrote the paper with assistance from BEK and GRS. All authors had final approval of the submitted manuscript.
PGC-1α is a transcriptional co-activator and master regulator of mitochondrial biogenesis. While extensively studied in skeletal and cardiac muscle, recent findings suggest that white adipose tissue PGC-1α plays an important role in regulating glucose homeostasis. The purpose of the present investigation was to evaluate the role of AMPK in regulating PGC-1α and mitochondrial enzymes in mouse epididymal and inguinal subcutaneous adipose tissue.
Mitochondrial protein content and norepinephrine and CL 316,243-induced PGC-1α mRNA expression were studied in mouse epididymal and inguinal adipose tissue from wild-type and AMPK β1−/− mice.
The protein content and phosphorylation of AMPKα was reduced in epididymal adipose tissue from AMPK β1−/− compared to WT mice, concomitant with decreases in PGC-1α and mitochondrial marker proteins. Norepinephrine and CL 316,243-mediated induction of PGC-1α were decreased in cultured epididymal adipose tissue from AMPK β1−/− relative to WT mice. In inguinal adipose tissue from AMPK β1−/− mice, mitochondrial marker protein content and norepinephrine and CL 316,243-mediated increases in PGC-1α were normal despite reductions in the content and phosphorylation of AMPKα.
Norepinephrine- and CL 316,243-mediated induction of PGC-1α and mitochondrial protein expression is regulated by AMPK in epididymal, but not inguinal adipose tissue.