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ARS Home » Northeast Area » Boston, Massachusetts » Jean Mayer Human Nutrition Research Center On Aging » Research » Publications at this Location » Publication #212686
Title: Perilipin regulates the thermogenic actions of norepinephrine in brown adipose tissue

Author
item SOUZA, SANDRA - TUFTS/HNRCA
item CHRISTOFFOLETE, MARCELO - BRIGHAM & WOMENS, HARVARD
item RIBEIRO, MIRIAM - MACKENZIE PRESBYTERIAN
item MIYOSHI, HIDEAKI - TUFTS/HNRCA
item STRISSEL, KATHERINE - TUFTS/HNRCA
item STANCHEVA, ZLATINA - TUFTS/HNRCA
item ROGERS, NICOLE - TUFTS/HNRCA
item D'EON, TARA - TUFTS/HNRCA, ELIXIR PHARM
item PERFIELD, JAMES - TUFTS.HNRCA
item IMACHI, HITOMI - TUFTS/HNRCA, KAGAWA UNIV
item OBIN, MARTIN - TUFTS/HNRCA
item BIANCO, ANTONIO - BRIGHAM & WOMENS, HARVARD
item Greenberg, Andrew

Submitted to: Journal of Lipid Research
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 3/15/2007
Publication Date: 3/30/2007
Citation: 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: 1273-79.

Interpretive Summary: In response to cold, a specific type of fat cell death called lipolysis of brown fat tissue provides fatty acid substrates to mitochondria for heat generation. This type of fat cell death is mediated by a protein associated with fat cells called perilipin. We investigated the role of perilipin in brown fat tissue heat generation using a mouse model in which a mutant form of perilipin is expressed in fat cells. Here, we show that despite normal mitochondrial activity, fat cell death is not found in the interscapular brown fat tissue of these mice which is located between the shoulder blades. This constraint is accompanied by a dramatic dulling of heat generation. Thus, perilipin is essential for fat cell death and heat generation in brown fat tissue. In addition, in the interscapular brown fat tissue of mice lacking perilipin, increased fat cell death is sufficient to support a rapid temperature increase comparable to that in wild-type mice. This observation suggests that there is/are one or more mechanisms, other than perilipin, that are required to initiate and/or sustain the interscapular brown fat tissue heat generation.

Technical 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 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 degrees celsius) 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.