Overexpression of the transcription factor Foxo4 is associated with rapid glucose clearance.
Leptin treatment ameliorates lipoatrophic diabetes in animal models and humans. Transgenic mice overexpressing leptin (LepTg) are lipoatrophic but not diabetic and thus represent a model for elucidating mechanisms of leptin-mediated glucose homeostasis. In this communication, we show that LepTg mice overexpress the forkhead transcription factor foxo4 in their remnant adipose tissue. To further characterize the role of foxo4 in adipose tissue, we generated transgenic mice overexpressing a constitutive active form of foxo4 (A3foxo4) under the control of the aP2 promoter/enhancer. aP2-A3foxo4 mice are not lipoatrophic but are able to clear glucose rapidly similar to LepTg mice. In addition, both LepTg and A3foxo4 mice show in their adipocytes increased AMP-activated protein kinase (AMPK) phosphorylation, suggesting a link between AMPK, glucose clearance, foxo4 and the leptin axis. These studies shed new light on mechanisms by which leptin treatment improves glucose disposal.
Department of Laboratory Medicine, University of California, San Francisco, CA 94107, USA.
Biao
B
Wang
Jun
J
Zhu
Khalid
K
Mounzih
Eric F
EF
Chehab
Yaohuang
Y
Ke
Farid F
FF
Chehab
D055372:AMP-Activated Protein Kinases / Q000378:metabolism; D017667:Adipocytes / Q000378:metabolism; D052436:Adipose Tissue, White / Q000201:enzymology; D000818:Animals; D018797:Cell Cycle Proteins; D004789:Enzyme Activation; D005260:Female; D051858:Forkhead Transcription Factors / Q000378:metabolism*; D005947:Glucose / Q000378:metabolism*; D005951:Glucose Tolerance Test; D048788:Growth and Development; D020738:Leptin / Q000378:metabolism; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D009154:Mutation / Q000235:genetics; D010766:Phosphorylation; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism
D018797:Cell Cycle Proteins; D051858:Forkhead Transcription Factors; C525394:FoxO4 protein, mouse; D020738:Leptin; D051057:Proto-Oncogene Proteins c-akt; D055372:AMP-Activated Protein Kinases; D005947:Glucose