Skip to main content
eScholarship
Open Access Publications from the University of California

UC Riverside

UC Riverside Electronic Theses and Dissertations bannerUC Riverside

CaMKKbeta/AMPK Negatively Regulates Adiposity

Abstract

Lipid synthesis and storage in adipose tissues contribute to energy homeostasis, which is inversely regulated by activated AMP-activated protein kinase (AMPK). Here, I report that Ca2+/calmodulin-dependent protein kinase kinase beta (CaMKKbeta) negatively regulates lipogenesis in adipocytes through its phosphorylation of AMPK. Specifically, the glucagon-activated CaMKKbeta/AMPK cascade inhibits acetyl-CoA carboxylase (ACC) activity through the phosphorylation of ACC both in vitro and in vivo. Fasting increases, whereas refeeding decreases, the phosphorylation of AMPK and ACC in CaMKKbeta+/+, but not in CaMKKbeta-/- mice. Under ad libitum feeding, the increased expression of sterol regulatory element binding protein-1c (SREBP-1c)-mediated lipogenic gene is concurrent with decreased phosphorylation of AMPK-regulated ACC in white adipose tissue (WAT) of CaMKKbeta-/- mice. In line with the inhibitory role of CaMKKbeta in lipid synthesis and storage, CaMKKbeta-/- mice exhibit increased body weight, adiposity, and adipocyte hypertrophy, although their appetite is comparable with the CaMKKbeta+/+ littermates. Additionally, metformin, an AMPK activator, does not increase the phosphorylation of AMPK and ACC in WAT of CaMKKbeta-/- mice. Thus, the CaMKKbeta/AMPK signaling is an important molecular event in physiological and pharmacological (e.g., metformin) regulation of adiposity.

Main Content
For improved accessibility of PDF content, download the file to your device.
Current View