Cell Metab. 2011 Oct 3. [Epub ahead of print]

Plac8 Is an Inducer of C/EBPβ Required for Brown Fat Differentiation,
Thermoregulation, and Control of Body Weight.

Jimenez-Preitner M, Berney X, Uldry M, Vitali A, Cinti S, Ledford JG, Thorens B.

Center for Integrative Genomics, University of Lausanne, CH-1015 Lausanne,
Switzerland.

Brown adipocytes oxidize fatty acids to produce heat in response to cold or to
excessive energy intake; stimulation of brown fat development and function may
thus counteract obesity. Brown adipogenesis requires activation of the
transcription factor C/EBPβ and recruitment of the zinc finger protein Prdm16,
but upstream inducers of these proteins are incompletely defined. Here, we show
that genetic inactivation of Plac8, a gene encoding an evolutionarily conserved
protein, induces cold intolerance, and late-onset obesity, as well as abnormal
morphology and impaired function of brown adipocytes. Using brown preadipocyte
lines we show that Plac8 is required for brown fat differentiation, that its
overexpression induces C/EBPβ and Prdm16, and that upon induction of
differentiation Plac8 associates with C/EBPβ and binds to the C/EBPβ promoter
to induce its transcription. Thus, Plac8 is a critical upstream regulator of
brown fat differentiation and function that acts, at least in part, by inducing
C/EBPβ expression.

PMID: 21982742  [PubMed - as supplied by publisher]