Now, Salk researchers have developed a new system that lets them study in more detail than ever exactly how, where and when AMPK carries out its molecular and therapeutic functions. In the paper, published January 2, 2019 in the journal Cell Reports, the Salk team uses the new model to activate AMPK in the livers of adult mice with fatty liver disease.
"This model will allow us to answer questions that scientists could not answer before," says Salk Professor and Salk Cancer Center Director Reuben Shaw, who led the new work. "It really gives us a new way to define the health benefits of this specific enzyme in a wide variety of diseases."
Protein - Kinase - AMPK - Master - Regulator
AMP-activated protein kinase, or AMPK, is known as a master regulator of metabolism. Cells activate AMPK when they are running low on energy, and AMPK is activated in tissues throughout the body following exercise or during calorie restriction. In response, AMPK alters the activity of many other genes and proteins, helping keep cells alive and functioning even when they're running low on fuel. In different tissues throughout the body and at different time points in development, AMPK likely has varying effects. Until now, the only way to study the specific impact of genetically increasing AMPK activity was to change its activity in an organism for its entire life, starting at embryogenesis.
"When AMPK is overactivated from the very beginning of embryogenesis, we don't know what effects it's having on normal development," says Daniel Garcia, a senior research associate at Salk and first author of the new paper.
Garcia - Shaw - Colleagues - Mouse - Version
So Garcia, Shaw and their colleagues enabled a mouse to have a special version of AMPK that lets the researchers activate the gene by feeding the adult mouse an antibiotic.
"The model we've developed is much more similar to what you would see in a...
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