[PDF][PDF] Hypothalamic CaMKK2 contributes to the regulation of energy balance

KA Anderson, TJ Ribar, F Lin, PK Noeldner, MF Green… - Cell metabolism, 2008 - cell.com
KA Anderson, TJ Ribar, F Lin, PK Noeldner, MF Green, MJ Muehlbauer, LA Witters…
Cell metabolism, 2008cell.com
Detailed knowledge of the pathways by which ghrelin and leptin signal to AMPK in
hypothalamic neurons and lead to regulation of appetite and glucose homeostasis is central
to the development of effective means to combat obesity. Here we identify CaMKK2 as a
component of one of these pathways, show that it regulates hypothalamic production of the
orexigenic hormone NPY, provide evidence that it functions as an AMPKα kinase in the
hypothalamus, and demonstrate that it forms a unique signaling complex with AMPKα and β …
Summary
Detailed knowledge of the pathways by which ghrelin and leptin signal to AMPK in hypothalamic neurons and lead to regulation of appetite and glucose homeostasis is central to the development of effective means to combat obesity. Here we identify CaMKK2 as a component of one of these pathways, show that it regulates hypothalamic production of the orexigenic hormone NPY, provide evidence that it functions as an AMPKα kinase in the hypothalamus, and demonstrate that it forms a unique signaling complex with AMPKα and β. Acute pharmacologic inhibition of CaMKK2 in wild-type mice, but not CaMKK2 null mice, inhibits appetite and promotes weight loss consistent with decreased NPY and AgRP mRNAs. Moreover, the loss of CaMKK2 protects mice from high-fat diet-induced obesity, insulin resistance, and glucose intolerance. These data underscore the potential of targeting CaMKK2 as a therapeutic intervention.
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