Loss of Akt1 in mice increases energy expenditure and protects against diet-induced obesity.
Akt is encoded by a gene family for which each isoform serves distinct but overlapping functions. Based on the phenotypes of the germ line gene disruptions, Akt1 has been associated with control of growth, whereas Akt2 has been linked to metabolic regulation. Here we show that Akt1 serves an unexpected role in the regulation of energy metabolism, as mice deficient for Akt1 exhibit protection from diet-induced obesity and its associated insulin resistance. Although skeletal muscle contributes most of the resting and exercising energy expenditure, muscle-specific deletion of Akt1 does not recapitulate the phenotype, indicating that the role of Akt1 in skeletal muscle is cell nonautonomous. These data indicate a previously unknown function of Akt1 in energy metabolism and provide a novel target for treatment of obesity.
The Institute for Diabetes, Obesity, and Metabolism, University of Pennsylvania, Philadelphia, Pennsylvania, USA.
Min
M
Wan
Rachael M
RM
Easton
Catherine E
CE
Gleason
Bobby R
BR
Monks
Kohjiro
K
Ueki
C Ronald
CR
Kahn
Morris J
MJ
Birnbaum
D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics* / Q000378:metabolism*; D000818:Animals; D004032:Diet; D004734:Energy Metabolism; D017353:Gene Deletion; D007328:Insulin / Q000378:metabolism; D007333:Insulin Resistance / Q000235:genetics; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D018482:Muscle, Skeletal / Q000378:metabolism; D009765:Obesity / Q000235:genetics* / Q000378:metabolism*
D048868:Adaptor Proteins, Signal Transducing; D007328:Insulin; C515963:Traf3ip2 protein, mouse