Induced adiposity and adipocyte hypertrophy in mice lacking the AMP-activated protein kinase-alpha2 subunit.
AMP-activated protein kinase (AMPK) is considered as a cellular energy sensor that regulates glucose and lipid metabolism by phosphorylating key regulatory enzymes. Despite the major role of adipose tissue in regulating energy partitioning in the organism, the role of AMPK in this tissue has not been addressed. In the present study, we subjected AMPKalpha2 knockout (KO) mice to a high-fat diet to examine the effect of AMPK on adipose tissue formation. Compared with the wild type, AMPKalpha2 KO mice exhibited increased body weight and fat mass. The increase in adipose tissue mass was due to the enlargement of the preexisting adipocytes with increased lipid accumulation. However, we did not observe any changes in adipocyte marker expression, such as peroxisome proliferator-activated receptor-gamma, CCAAT/enhancer-binding protein alpha (C/EBPalpha) and adipocyte fatty acid-binding protein (aFABP/aP2), or total cell number. Unlike impaired glucose homeostasis observed on normal diet feeding, when fed a high-fat diet AMPKalpha2 KO mice did not show differences in glucose tolerance and insulin sensitivity compared with wild-type mice. Our results suggest that the increase in lipid storage in adipose tissue in AMPKalpha2 KO mice may have protected these mice from further impairment of glucose homeostasis that normally accompanies high-fat feeding. Our study also demonstrates that lack of AMPKalpha2 subunit may be a factor contributing to the development of obesity.
Villena
Josep A
JA
Department of Nutritional Sciences and Toxicology, University of California, Berkeley, CA 94720. hsul@nature.berkeley.edu
Viollet
Benoit
B
Andreelli
Fabrizzio
F
Kahn
Axel
A
Vaulont
Sophie
S
Sul
Hei Sook
HS
D055372:AMP-Activated Protein Kinases; D017667:Adipocytes / Q000201:enzymology* / Q000473:pathology*; D000273:Adipose Tissue / Q000378:metabolism / Q000473:pathology; D000818:Animals; D001835:Body Weight; D048429:Cell Size; D004041:Dietary Fats / Q000494:pharmacology; D005951:Glucose Tolerance Test; D006984:Hypertrophy; D007333:Insulin Resistance; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009097:Multienzyme Complexes / Q000235:genetics* / Q000378:metabolism*; D009765:Obesity / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology*; D017346:Protein Serine-Threonine Kinases / Q000235:genetics* / Q000378:metabolism*; D014280:Triglycerides / Q000378:metabolism
D004041:Dietary Fats; D009097:Multienzyme Complexes; D014280:Triglycerides; D017346:Protein Serine-Threonine Kinases; D055372:AMP-Activated Protein Kinases