Abstract In response to cold, norepinephrine (NE)- induced triacylglycerol hydrolysis (lipolysis) in adipocytes of brown adipose tissue (BAT) provides fatty acid substrates to mitochondria for heat generation (adaptive thermogen- esis). NE-induced lipolysis is mediated by protein kinase A (PKA)-dependent phosphorylation of perilipin, a lipid droplet-associated protein that is the major regulator of lipolysis. We investigated the role of perilipin PKA phos- phorylation in BAT NE-stimulated thermogenesis using a novel mouse model in which a mutant form of perilipin, lacking all six PKA phosphorylation sites, is expressed in adipocytes of perilipin knockout (Peri KO) mice. Here, we show that despite a normal mitochondrial respiratory capacity, NE-induced lipolysis is abrogated in the inter- scapular brown adipose tissue (IBAT) of these mice. This lipolytic constraint is accompanied by a dramatic blunting (?70%) of the in vivo thermal response to NE. Thus, in the presence of perilipin, PKA-mediated perilipin phosphory- lation is essential for NE-dependent lipolysis and full adaptive thermogenesis in BAT. In IBAT of Peri KO mice, increased basal lipolysis attributable to the absence of peri- lipin is sufficient to support a rapid NE-stimulated tem- perature increase (?3.0jC) comparable to that in wild-type mice. This observation suggests that one or more NE- dependent mechanism downstream of perilipin phosphor- ylation is required to initiate and/or sustain the IBAT thermal response.—Souza, S. C., M. A. Christoffolete, M. O. Ribeiro, H. Miyoshi, K. J. Strissel, Z. S. Stancheva, N. H. Rogers, T. M. D_Eon, J. W. Perfield, II, H. Imachi, M. S. Obin, A. C. Bianco, and A. S. Greenberg. Perilipin regulates the thermogenic actions of norepinephrine in brown adi- pose tissue.

Perilipin regulates the thermogenic actions of norepinephrine in brown adipose tissue.

Sandra C. Souza, Marcelo A. Christoffolete, Miriam O. Ribeiro, Hideaki Miyoshi, Katherine J. Strissel, Zlatina S. Stancheva, Nicole H. Rogers, Tara M. D’Eon, James W. Perfield, Hitomi Imachi, Martin S. Obin, Antonio C. Bianco and Andrew S. Greenberg. Journal of Lipid Research. March 30, 2007. doi: 10.1194/jlr.M700047-JLR200

Download PDF