PMID- 25856396
OWN - NLM
STAT- MEDLINE
DCOM- 20151224
LR  - 20210514
IS  - 1932-6203 (Electronic)
IS  - 1932-6203 (Linking)
VI  - 10
IP  - 4
DP  - 2015
TI  - Opposing activity changes in AMP deaminase and AMP-activated protein kinase in 
      the hibernating ground squirrel.
PG  - e0123509
LID - 10.1371/journal.pone.0123509 [doi]
LID - e0123509
AB  - 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 beta-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 beta-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 beta-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.
FAU - Lanaspa, Miguel A
AU  - Lanaspa MA
AD  - Division of Renal Diseases and Hypertension, University of Colorado Denver, 
      Aurora, CO, 80045, United States of America.
FAU - Epperson, L Elaine
AU  - Epperson LE
AD  - Department of Cell and Developmental Biology, Aurora, CO, 80045, United States of 
      America.
FAU - Li, Nanxing
AU  - Li N
AD  - Division of Renal Diseases and Hypertension, University of Colorado Denver, 
      Aurora, CO, 80045, United States of America.
FAU - Cicerchi, Christina
AU  - Cicerchi C
AD  - Division of Renal Diseases and Hypertension, University of Colorado Denver, 
      Aurora, CO, 80045, United States of America.
FAU - Garcia, Gabriela E
AU  - Garcia GE
AD  - Division of Renal Diseases and Hypertension, University of Colorado Denver, 
      Aurora, CO, 80045, United States of America.
FAU - Roncal-Jimenez, Carlos A
AU  - Roncal-Jimenez CA
AD  - Division of Renal Diseases and Hypertension, University of Colorado Denver, 
      Aurora, CO, 80045, United States of America.
FAU - Trostel, Jessica
AU  - Trostel J
AD  - Division of Renal Diseases and Hypertension, University of Colorado Denver, 
      Aurora, CO, 80045, United States of America.
FAU - Jain, Swati
AU  - Jain S
AD  - Division of Renal Diseases and Hypertension, University of Colorado Denver, 
      Aurora, CO, 80045, United States of America.
FAU - Mant, Colin T
AU  - Mant CT
AD  - Department of Biochemistry and Molecular Genetics, Aurora, CO, 80045, United 
      States of America.
FAU - Rivard, Christopher J
AU  - Rivard CJ
AD  - Division of Renal Diseases and Hypertension, University of Colorado Denver, 
      Aurora, CO, 80045, United States of America.
FAU - Ishimoto, Takuji
AU  - Ishimoto T
AD  - Division of Renal Diseases and Hypertension, University of Colorado Denver, 
      Aurora, CO, 80045, United States of America.
FAU - Shimada, Michiko
AU  - Shimada M
AD  - Division of Renal Diseases and Hypertension, University of Colorado Denver, 
      Aurora, CO, 80045, United States of America.
FAU - Sanchez-Lozada, Laura Gabriela
AU  - Sanchez-Lozada LG
AD  - 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.
FAU - Nakagawa, Takahiko
AU  - Nakagawa T
AD  - Division of Renal Diseases and Hypertension, University of Colorado Denver, 
      Aurora, CO, 80045, United States of America.
FAU - Jani, Alkesh
AU  - Jani A
AD  - Division of Renal Diseases and Hypertension, University of Colorado Denver, 
      Aurora, CO, 80045, United States of America.
FAU - Stenvinkel, Peter
AU  - Stenvinkel P
AD  - Division of Renal Medicine, Department of Clinical Intervention and Technology, 
      Karolinska Institutet, Stockholm, Sweden.
FAU - Martin, Sandra L
AU  - Martin SL
AD  - Department of Cell and Developmental Biology, Aurora, CO, 80045, United States of 
      America.
FAU - Johnson, Richard J
AU  - Johnson RJ
AD  - 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.
LA  - eng
GR  - RC4 DK90859/DK/NIDDK NIH HHS/United States
GR  - R01 HL068607/HL/NHLBI NIH HHS/United States
GR  - R01 DK082509/DK/NIDDK NIH HHS/United States
GR  - HL68607/HL/NHLBI NIH HHS/United States
GR  - R01 HL089049/HL/NHLBI NIH HHS/United States
GR  - HL089049/HL/NHLBI NIH HHS/United States
GR  - RC4 DK090859/DK/NIDDK NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
DEP - 20150409
PL  - United States
TA  - PLoS One
JT  - PloS one
JID - 101285081
RN  - 0 (Fatty Acids)
RN  - EC 2.7.11.31 (AMP-Activated Protein Kinases)
RN  - EC 3.5.4.6 (AMP Deaminase)
RN  - IY9XDZ35W2 (Glucose)
SB  - IM
MH  - AMP Deaminase/*metabolism
MH  - AMP-Activated Protein Kinases/*metabolism
MH  - Adipose Tissue/*metabolism
MH  - Animals
MH  - Fatty Acids/metabolism
MH  - Glucose/metabolism
MH  - Hibernation/genetics/*physiology
MH  - Lipid Metabolism/genetics
MH  - Liver/metabolism/physiology
MH  - Oxidation-Reduction
MH  - Sciuridae/metabolism/physiology
MH  - Seasons
PMC - PMC4391924
COIS- Competing Interests: Drs MAL, CJR, GEG and RJJ are listed as inventors on a 
      patent for the use of AMPD2 inhibitors to treat obesity and insulin resistance 
      (US 8,697, 628). MAL, CJR, LGSL, CARJ and RJJ are also members of Colorado 
      Research Partners LLC that is interested in developing novel treatments for 
      obesity. There are no further patents, products in development or marketed 
      products to declare. This does not alter the authors' adherence to all the PLOS 
      ONE policies on sharing data and materials, as detailed online in the guide for 
      authors.
EDAT- 2015/04/10 06:00
MHDA- 2015/12/25 06:00
PMCR- 2015/04/09
CRDT- 2015/04/10 06:00
PHST- 2014/05/19 00:00 [received]
PHST- 2015/03/04 00:00 [accepted]
PHST- 2015/04/10 06:00 [entrez]
PHST- 2015/04/10 06:00 [pubmed]
PHST- 2015/12/25 06:00 [medline]
PHST- 2015/04/09 00:00 [pmc-release]
AID - PONE-D-14-22309 [pii]
AID - 10.1371/journal.pone.0123509 [doi]
PST - epublish
SO  - PLoS One. 2015 Apr 9;10(4):e0123509. doi: 10.1371/journal.pone.0123509. 
      eCollection 2015.