Berardinelli-Seip congenital lipodystrophy 2 regulates adipocyte lipolysis, browning, and energy balance in adult animals.
Mutations in BSCL2/SEIPIN cause Berardinelli-Seip congenital lipodystrophy type 2 (BSCL2), but the mechanisms whereby Bscl2 regulates adipose tissue function are unclear. Here, we generated adipose tissue (mature) Bscl2 knockout (Ad-mKO) mice, in which Bscl2 was specifically ablated in adipocytes of adult animals, to investigate the impact of acquired Bscl2 deletion on adipose tissue function and energy balance. Ad-mKO mice displayed reduced adiposity and were protected against high fat diet-induced obesity, but not insulin resistance or hepatic steatosis. Gene expression profiling and biochemical assays revealed increased lipolysis and fatty acid oxidation in white adipose tissue (WAT) and brown adipose tissue , as well as browning of WAT, owing to induction of cAMP/protein kinase A signaling upon Bscl2 deletion. Interestingly, Bscl2 deletion reduced food intake and downregulated adipose β3-adrenergic receptor (ADRB3) expression. Impaired ADRB3 signaling partially offsets upregulated browning-induced energy expenditure and thermogenesis in Ad-mKO mice housed at ambient temperature. However, this counter-regulatory response was abrogated under thermoneutral conditions, resulting in even greater body mass loss in Ad-mKO mice. These findings suggest that Bscl2 regulates adipocyte lipolysis and β-adrenergic signaling to produce complex effects on adipose tissues and whole-body energy balance.
Department of Physiology, Georgia Regents University, Augusta, GA 30912.
Hongyi
H
Zhou
Department of Physiology, Georgia Regents University, Augusta, GA 30912.
Xinnuo
X
Lei
Vascular Biology Center, Georgia Regents University, Augusta, GA 30912.
Tyler
T
Benson
Vascular Biology Center, Georgia Regents University, Augusta, GA 30912.
James
J
Mintz
Georgia Prevention Institute, Department of Pediatrics, Georgia Regents University, Augusta, GA 30912.
Xiaojing
X
Xu
Department of Physiology, Georgia Regents University, Augusta, GA 30912.
Ruth B
RB
Harris
Vascular Biology Center, Georgia Regents University, Augusta, GA 30912.
Neal L
NL
Weintraub
Georgia Prevention Institute, Department of Pediatrics, Georgia Regents University, Augusta, GA 30912.
Xiaoling
X
Wang
Department of Physiology, Georgia Regents University, Augusta, GA 30912.
Weiqin
W
Chen
D017667:Adipocytes / Q000378:metabolism*; D002001:Adipose Tissue, Brown / Q000378:metabolism*; D052436:Adipose Tissue, White / Q000378:metabolism*; D000818:Animals; D059305:Diet, High-Fat; D004195:Disease Models, Animal; D004734:Energy Metabolism; D005234:Fatty Liver / Q000378:metabolism; D044388:GTP-Binding Protein gamma Subunits; D020962:Heterotrimeric GTP-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D007333:Insulin Resistance; D050356:Lipid Metabolism; D052497:Lipodystrophy, Congenital Generalized / Q000235:genetics / Q000378:metabolism*; D008066:Lipolysis; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D022702:Receptors, Adrenergic, beta-3 / Q000378:metabolism; D014280:Triglycerides / Q000378:metabolism
C115783:Bscl2 protein, mouse; D044388:GTP-Binding Protein gamma Subunits; D022702:Receptors, Adrenergic, beta-3; D014280:Triglycerides; D020962:Heterotrimeric GTP-Binding Proteins
adipose tissue; beta-oxidation; lipolysis and fatty acid metabolism; obesity; triglycerides