title: Role of adipose and hepatic atypical protein kinase C lambda (PKCλ) in the development of obesity and glucose intolerance.
abstract: PKCλ, an atypical member of the multifunctional protein kinase C family, has been implicated in the regulation of insulin-stimulated glucose transport and of the intracellular immune response. To further elucidate the role of this cellular regulator in diet-induced obesity and insulin resistance, we generated both liver (PKC-Alb) and adipose tissue (PKC-Ap2) specific knockout mice. Body weight, fat mass, food intake, glucose homeostasis and energy expenditure were evaluated in mice maintained on either chow or high fat diet (HFD). Ablation of PKCλ from the adipose tissue resulted in mice that were indistinguishable from their wild-type littermates. However, PKC-Alb mice were resistant to diet-induced obesity (DIO). Surprisingly this DIO resistance was not associated with either a reduction in caloric intake or an increase in energy expenditure as compared with their wild-type littermates. Furthermore, these mice displayed an improvement in glucose tolerance. When maintained on chow diet, these mice were similar to wild types in respect to body weight and fat mass, yet insulin sensitivity was impaired compared with wt littermates. Taken together these data suggest that hepatic PKCλ is modulating insulin-mediated glucose turnover and response to high fat diet feeding, thus offering a deeper understanding of an important target for anti-obesity therapeutics.
authors.affiliation: Division of Endocrinology; Department of Internal Medicine; Obesity Research Center; Metabolic Diseases Institute; University of Cincinnati; Cincinnati, OH USA.
authors.forename: Kirk M
authors.initials: KM
authors.lastname: Habegger
authors.forename: Daniela
authors.initials: D
authors.lastname: Matzke
authors.forename: Nickki
authors.initials: N
authors.lastname: Ottaway
authors.forename: Jazzminn
authors.initials: J
authors.lastname: Hembree
authors.forename: Jenna
authors.initials: J
authors.lastname: Holland
authors.forename: Christine
authors.initials: C
authors.lastname: Raver
authors.forename: Johannes
authors.initials: J
authors.lastname: Mansfeld
authors.forename: Timo D
authors.initials: TD
authors.lastname: Müller
authors.forename: Diego
authors.initials: D
authors.lastname: Perez-Tilve
authors.forename: Paul T
authors.initials: PT
authors.lastname: Pfluger
authors.forename: Sang Jun
authors.initials: SJ
authors.lastname: Lee
authors.forename: Maria
authors.initials: M
authors.lastname: Diaz-Meco
authors.forename: Jorge
authors.initials: J
authors.lastname: Moscat
authors.forename: Michael
authors.initials: M
authors.lastname: Leitges
authors.forename: Matthias H
authors.initials: MH
authors.lastname: Tschöp
authors.forename: Susanna M
authors.initials: SM
authors.lastname: Hofmann
keywords: atypical protein kinase C-lambda; diet induced obesity; energy expenditure; glucose tolerance; insulin resistance