title: Opposing activity changes in AMP deaminase and AMP-activated protein kinase in the hibernating ground squirrel.
abstract: Hibernating animals develop fatty liver when active in summertime and undergo a switch to a fat oxidation state in the winter. We hypothesized that this switch might be determined by AMP and the dominance of opposing effects: metabolism through AMP deaminase (AMPD2) (summer) and activation of AMP-activated protein kinase (AMPK) (winter). Liver samples were obtained from 13-lined ground squirrels at different times during the year, including summer and multiples stages of winter hibernation, and fat synthesis and β-fatty acid oxidation were evaluated. Changes in fat metabolism were correlated with changes in AMPD2 activity and intrahepatic uric acid (downstream product of AMPD2), as well as changes in AMPK and intrahepatic β-hydroxybutyrate (a marker of fat oxidation). Hepatic fat accumulation occurred during the summer with relatively increased enzymes associated with fat synthesis (FAS, ACL and ACC) and decreased enoyl CoA hydratase (ECH1) and carnitine palmitoyltransferase 1A (CPT1A), rate limiting enzymes of fat oxidation. In summer, AMPD2 activity and intrahepatic uric acid levels were high and hepatic AMPK activity was low. In contrast, the active phosphorylated form of AMPK and β-hydroxybutyrate both increased during winter hibernation. Therefore, changes in AMPD2 and AMPK activity were paralleled with changes in fat synthesis and fat oxidation rates during the summer-winter cycle. These data illuminate the opposing forces of metabolism of AMP by AMPD2 and its availability to activate AMPK as a switch that governs fat metabolism in the liver of hibernating ground squirrel.
authors: Division of Renal Diseases and Hypertension, University of Colorado Denver, Aurora, CO, 80045, United States of America.
authors: Miguel A
authors: MA
authors: Lanaspa
authors: Department of Cell and Developmental Biology, Aurora, CO, 80045, United States of America.
authors: L Elaine
authors: LE
authors: Epperson
authors: Division of Renal Diseases and Hypertension, University of Colorado Denver, Aurora, CO, 80045, United States of America.
authors: Nanxing
authors: N
authors: Li
authors: Division of Renal Diseases and Hypertension, University of Colorado Denver, Aurora, CO, 80045, United States of America.
authors: Christina
authors: C
authors: Cicerchi
authors: Division of Renal Diseases and Hypertension, University of Colorado Denver, Aurora, CO, 80045, United States of America.
authors: Gabriela E
authors: GE
authors: Garcia
authors: Division of Renal Diseases and Hypertension, University of Colorado Denver, Aurora, CO, 80045, United States of America.
authors: Carlos A
authors: CA
authors: Roncal-Jimenez
authors: Division of Renal Diseases and Hypertension, University of Colorado Denver, Aurora, CO, 80045, United States of America.
authors: Jessica
authors: J
authors: Trostel
authors: Division of Renal Diseases and Hypertension, University of Colorado Denver, Aurora, CO, 80045, United States of America.
authors: Swati
authors: S
authors: Jain
authors: Department of Biochemistry and Molecular Genetics, Aurora, CO, 80045, United States of America.
authors: Colin T
authors: CT
authors: Mant
authors: Division of Renal Diseases and Hypertension, University of Colorado Denver, Aurora, CO, 80045, United States of America.
authors: Christopher J
authors: CJ
authors: Rivard
authors: Division of Renal Diseases and Hypertension, University of Colorado Denver, Aurora, CO, 80045, United States of America.
authors: Takuji
authors: T
authors: Ishimoto
authors: Division of Renal Diseases and Hypertension, University of Colorado Denver, Aurora, CO, 80045, United States of America.
authors: Michiko
authors: M
authors: Shimada
authors: Division of Renal Diseases and Hypertension, University of Colorado Denver, Aurora, CO, 80045, United States of America; Laboratory of Renal Physiopathology and Nephrology Dept, INC Ignacio Chavez, Mexico City, Mexico.
authors: Laura Gabriela
authors: LG
authors: Sanchez-Lozada
authors: Division of Renal Diseases and Hypertension, University of Colorado Denver, Aurora, CO, 80045, United States of America.
authors: Takahiko
authors: T
authors: Nakagawa
authors: Division of Renal Diseases and Hypertension, University of Colorado Denver, Aurora, CO, 80045, United States of America.
authors: Alkesh
authors: A
authors: Jani
authors: Division of Renal Medicine, Department of Clinical Intervention and Technology, Karolinska Institutet, Stockholm, Sweden.
authors: Peter
authors: P
authors: Stenvinkel
authors: Department of Cell and Developmental Biology, Aurora, CO, 80045, United States of America.
authors: Sandra L
authors: SL
authors: Martin
authors: Division of Renal Diseases and Hypertension, University of Colorado Denver, Aurora, CO, 80045, United States of America; Division of Nephrology, Eastern Colorado Health System, Department of Veteran Affairs, Denver, CO, United States of America.
authors: Richard J
authors: RJ
authors: Johnson
mesh_terms: D000659:AMP Deaminase / Q000378:metabolism*; D055372:AMP-Activated Protein Kinases / Q000378:metabolism*; D000273:Adipose Tissue / Q000378:metabolism*; D000818:Animals; D005227:Fatty Acids / Q000378:metabolism; D005947:Glucose / Q000378:metabolism; D006605:Hibernation / Q000235:genetics / Q000502:physiology*; D050356:Lipid Metabolism / Q000235:genetics; D008099:Liver / Q000378:metabolism / Q000502:physiology; D010084:Oxidation-Reduction; D012589:Sciuridae / Q000378:metabolism / Q000502:physiology; D012621:Seasons
chemical_list: D005227:Fatty Acids; D055372:AMP-Activated Protein Kinases; D000659:AMP Deaminase; D005947:Glucose