Chronic activation of AMP-activated protein kinase-alpha1 in liver leads to decreased adiposity in mice.
To assess the metabolic effects of chronic activation of AMP-activated protein kinase (AMPK) in liver, we generated a new transgenic (Tg) mouse model expressing constitutively active (CA)-AMPK-alpha1 in liver. In the short-term activation, the TgCA-AMPK-alpha1 mice exhibited minimal phenotype, but the Tg liver had elevated sterol regulatory element-binding protein (SREBP)-2 mRNA level and a parallel increase in transcripts of its target genes. UCP2 mRNA level was elevated. In the long-term activation, the TgCA-AMPK-alpha1 mice had markedly reduced white fat mass. The Tg liver had reduced mRNA expression of SREBP-1c and its target genes. Remarkably, the Tg mice were resistant to a high-fat diet-induced obesity. These data suggest that short-term chronic activation of AMPK-alpha1 in liver leads to compensatory increase in lipogenic gene expression due to increased SREBP-2 expression, and long-term chronic activation of AMPK-alpha1 decreases expression of SREBP-1c and its target genes, which results in reduced fat storage.
Yang
Jian
J
Department of Physiology, The University of South Alabama College of Medicine, MSB 3074, 307 University Boulevard, Mobile, AL 36688-0002, USA. jyang@usouthal.edu
Maika
Shanna
S
Craddock
Lauren
L
King
Judy A
JA
Liu
Zhi-Mei
ZM
D055372:AMP-Activated Protein Kinases; D052436:Adipose Tissue, White / Q000473:pathology; D050154:Adiposity / Q000235:genetics; D000818:Animals; D004041:Dietary Fats / Q000008:administration & dosage; D004195:Disease Models, Animal; D004789:Enzyme Activation; D005786:Gene Expression Regulation; D050155:Lipogenesis / Q000235:genetics; D008099:Liver / Q000201:enzymology* / Q000473:pathology; D051379:Mice; D008822:Mice, Transgenic; D009097:Multienzyme Complexes / Q000235:genetics / Q000378:metabolism*; D009765:Obesity / Q000201:enzymology* / Q000235:genetics; D010641:Phenotype; D017346:Protein Serine-Threonine Kinases / Q000235:genetics / Q000378:metabolism*; D051381:Rats; D051782:Sterol Regulatory Element Binding Protein 2 / Q000378:metabolism
D004041:Dietary Fats; D009097:Multienzyme Complexes; C497391:Srebf2 protein, mouse; D051782:Sterol Regulatory Element Binding Protein 2; D017346:Protein Serine-Threonine Kinases; D055372:AMP-Activated Protein Kinases