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, Andrew S. Greenberg

Research output: Contribution to journalArticle

28 Scopus citations

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 thermogenesis). 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 phosphorylation 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 interscapular 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 phosphorylation 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 perilipin is sufficient to support a rapid NE-stimulated temperature increase (∼3.0°C) comparable to that in wild-type mice. This observation suggests that one or more NE-dependent mechanism downstream of perilipin phosphorylation is required to initiate and/or sustain the IBAT thermal response.

Original languageEnglish (US)
Pages (from-to)1273-1279
Number of pages7
JournalJournal of Lipid Research
Volume48
Issue number6
DOIs
StatePublished - Jun 1 2007

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Keywords

  • Brown adipocytes
  • Norepinephrine-induced thermal response
  • Protein kinase A-stimulated lipolysis

ASJC Scopus subject areas

  • Endocrinology

Cite this

Souza, S. C., Christoffolete, M. A., Ribeiro, M. O., Miyoshi, H., Strissel, K. J., Stancheva, Z. S., Rogers, N. H., D'Eon, T. M., Perfield, J. W., Imachi, H., Obin, M. S., Bianco, A. C., & Greenberg, A. S. (2007). Perilipin regulates the thermogenic actions of norepinephrine in brown adipose tissue. Journal of Lipid Research, 48(6), 1273-1279. https://doi.org/10.1194/jlr.M700047-JLR200