Hypothalamic CaMKK2 contributes to the regulation of energy balance.

Published

Journal Article

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 AMPKalpha kinase in the hypothalamus, and demonstrate that it forms a unique signaling complex with AMPKalpha and beta. 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.

Full Text

Duke Authors

Cited Authors

  • Anderson, KA; Ribar, TJ; Lin, F; Noeldner, PK; Green, MF; Muehlbauer, MJ; Witters, LA; Kemp, BE; Means, AR

Published Date

  • May 2008

Published In

Volume / Issue

  • 7 / 5

Start / End Page

  • 377 - 388

PubMed ID

  • 18460329

Pubmed Central ID

  • 18460329

Electronic International Standard Serial Number (EISSN)

  • 1932-7420

Digital Object Identifier (DOI)

  • 10.1016/j.cmet.2008.02.011

Language

  • eng

Conference Location

  • United States