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Hypothalamic CaMKK2 contributes to the regulation of energy balance.

Publication ,  Journal Article
Anderson, KA; Ribar, TJ; Lin, F; Noeldner, PK; Green, MF; Muehlbauer, MJ; Witters, LA; Kemp, BE; Means, AR
Published in: Cell Metab
May 2008

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.

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Published In

Cell Metab

DOI

EISSN

1932-7420

Publication Date

May 2008

Volume

7

Issue

5

Start / End Page

377 / 388

Location

United States

Related Subject Headings

  • Weight Loss
  • Transfection
  • RNA, Messenger
  • Protein Kinases
  • Neuropeptide Y
  • Naphthalimides
  • Mice, Knockout
  • Mice, Inbred C57BL
  • Mice
  • Male
 

Citation

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Anderson, K. A., Ribar, T. J., Lin, F., Noeldner, P. K., Green, M. F., Muehlbauer, M. J., … Means, A. R. (2008). Hypothalamic CaMKK2 contributes to the regulation of energy balance. Cell Metab, 7(5), 377–388. https://doi.org/10.1016/j.cmet.2008.02.011
Anderson, Kristin A., Thomas J. Ribar, Fumin Lin, Pamela K. Noeldner, Michelle F. Green, Michael J. Muehlbauer, Lee A. Witters, Bruce E. Kemp, and Anthony R. Means. “Hypothalamic CaMKK2 contributes to the regulation of energy balance.Cell Metab 7, no. 5 (May 2008): 377–88. https://doi.org/10.1016/j.cmet.2008.02.011.
Anderson KA, Ribar TJ, Lin F, Noeldner PK, Green MF, Muehlbauer MJ, et al. Hypothalamic CaMKK2 contributes to the regulation of energy balance. Cell Metab. 2008 May;7(5):377–88.
Anderson, Kristin A., et al. “Hypothalamic CaMKK2 contributes to the regulation of energy balance.Cell Metab, vol. 7, no. 5, May 2008, pp. 377–88. Pubmed, doi:10.1016/j.cmet.2008.02.011.
Anderson KA, Ribar TJ, Lin F, Noeldner PK, Green MF, Muehlbauer MJ, Witters LA, Kemp BE, Means AR. Hypothalamic CaMKK2 contributes to the regulation of energy balance. Cell Metab. 2008 May;7(5):377–388.
Journal cover image

Published In

Cell Metab

DOI

EISSN

1932-7420

Publication Date

May 2008

Volume

7

Issue

5

Start / End Page

377 / 388

Location

United States

Related Subject Headings

  • Weight Loss
  • Transfection
  • RNA, Messenger
  • Protein Kinases
  • Neuropeptide Y
  • Naphthalimides
  • Mice, Knockout
  • Mice, Inbred C57BL
  • Mice
  • Male