Berardinelli-Seip Congenital Lipodystrophy 2/Seipin Is Not Required for Brown Adipogenesis but Regulates Brown Adipose Tissue Development and Function
AffiliationUniv Arizona, Dept Med, Div Translat & Regenerat Med
MetadataShow full item record
PublisherAMER SOC MICROBIOLOGY
CitationBerardinelli-Seip Congenital Lipodystrophy 2/Seipin Is Not Required for Brown Adipogenesis but Regulates Brown Adipose Tissue Development and Function 2016, 36 (15):2027 Molecular and Cellular Biology
JournalMolecular and Cellular Biology
RightsCopyright © 2016, American Society for Microbiology. All Rights Reserved.
Collection InformationThis item from the UA Faculty Publications collection is made available by the University of Arizona with support from the University of Arizona Libraries. If you have questions, please contact us at email@example.com.
AbstractBrown adipose tissue (BAT) plays a unique role in regulating whole-body energy homeostasis by dissipating energy through thermogenic uncoupling. Berardinelli-Seip congenital lipodystrophy (BSCL) type 2 (BSCL2; also known as seipin) is a lipodystrophy-associated endoplasmic reticulum membrane protein essential for white adipocyte differentiation. Whether BSCL2 directly participates in brown adipocyte differentiation, development, and function, however, is unknown. We show that BSCL2 expression is increased during brown adipocyte differentiation. Its deletion does not impair the classic brown adipogenic program but rather induces premature activation of differentiating brown adipocytes through cyclic AMP (cAMP)/protein kinase A (PKA)-mediated lipolysis and fatty acid and glucose oxidation, as well as uncoupling. cAMP/PKA signaling is physiologically activated during neonatal BAT development in wild-type mice and greatly potentiated in mice with genetic deletion of Bscl2 in brown progenitor cells, leading to reduced BAT mass and lipid content during neonatal brown fat formation. However, prolonged overactivation of cAMP/PKA signaling during BAT development ultimately causes apoptosis of brown adipocytes through inflammation, resulting in BAT atrophy and increased overall adiposity in adult mice. These findings reveal a key cell-autonomous role for BSCL2 in controlling BAT mass/activity and provide novel insights into therapeutic strategies targeting cAMP/PKA signaling to regulate brown adipocyte function, viability, and metabolic homeostasis.
Note6 Month Embargo.
VersionFinal published version
SponsorsAmerican Heart Association (AHA) [12SDG9080000]; HHS | NIH | National Heart, Lung, and Blood Institute (NHLBI) [HL112640, HL132182, HL126949]