Evidence for the role of AMPK in regulating PGC-1 alpha expression and mitochondrial proteins in mouse epididymal adipose tissue

Objective 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. Methods 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. Results 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. Conclusions 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.