Evidence for the Role of AMPK in Regulating PGC-1 Alpha Expression and Mitochondrial Proteins in Mouse Epididymal Adipose Tissue

Objective: PGC-1 alpha 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-1 alpha plays an important role in regulating glucose homeostasis. The purpose of the present investigation was to evaluate the role of AMPK in regulating PGC-1 alpha and mitochondrial enzymes in mouse epididymal and inguinal subcutaneous adipose tissue. Methods: Mitochondrial protein content and norepinephrine and CL 316,243-induced PGC-1 alpha mRNA expression were studied in mouse epididymal and inguinal adipose tissue from wild-type and AMPK ss 1(-/-) mice. Results: The protein content and phosphorylation of AMPK alpha was reduced in epididymal adipose tissue from AMPK ss 1(-/-) compared to WT mice, concomitant with decreases in PGC-1 alpha and mitochondrial marker proteins. Norepinephrine and CL 316,243-mediated induction of PGC-1 alpha were decreased in cultured epididymal adipose tissue from AMPK ss(-/-) relative to WT mice. In inguinal adipose tissue from AMPK ss 1(-/-) mice, mitochondrial marker protein content and norepinephrine and CL 316,243-mediated increases in PGC-1 alpha were normal despite reductions in the content and phosphorylation of AMPKa. Conclusions: Norepinephrine-and CL 316,243-mediated induction of PGC-1 alpha and mitochondrial protein expression is regulated by AMPK in epididymal, but not inguinal adipose tissue.