title: Altered lipid metabolism in residual white adipose tissues of Bscl2 deficient mice.
abstract: Mutations in BSCL2 underlie human congenital generalized lipodystrophy type 2 disease. We previously reported that Bscl2 (-/-) mice develop lipodystrophy of white adipose tissue (WAT) due to unbridled lipolysis. The residual epididymal WAT (EWAT) displays a browning phenotype with much smaller lipid droplets (LD) and higher expression of brown adipose tissue marker proteins. Here we used targeted lipidomics and gene expression profiling to analyze lipid profiles as well as genes involved in lipid metabolism in WAT of wild-type and Bscl2(-/-) mice. Analysis of total saponified fatty acids revealed that the residual EWAT of Bscl2(-/-) mice contained a much higher proportion of oleic 18:1n9 acid concomitant with a lower proportion of palmitic 16:0 acid, as well as increased n3- polyunsaturated fatty acids (PUFA) remodeling. The acyl chains in major species of triacylglyceride (TG) and diacylglyceride (DG) in the residual EWAT of Bscl2(-/-) mice were also enriched with dietary fatty acids. These changes could be reflected by upregulation of several fatty acid elongases and desaturases. Meanwhile, Bscl2(-/-) adipocytes from EWAT had increased gene expression in lipid uptake and TG synthesis but not de novo lipogenesis. Both mitochondria and peroxisomal β-oxidation genes were also markedly increased in Bscl2(-/-) adipocytes, highlighting that these machineries were accelerated to shunt the lipolysis liberated fatty acids through uncoupling to dissipate energy. The residual subcutaneous white adipose tissue (ScWAT) was not browning but displays similar changes in lipid metabolism. Overall, our data emphasize that, other than being essential for adipocyte differentiation, Bscl2 is also important in fatty acid remodeling and energy homeostasis.
authors.affiliation: Department of Physiology, Medical College of Georgia at Georgia Regents University, Augusta, Georgia, United States of America.
authors.forename: Weiqin
authors.initials: W
authors.lastname: Chen
authors.affiliation: Department of Physiology, Medical College of Georgia at Georgia Regents University, Augusta, Georgia, United States of America.
authors.forename: Hongyi
authors.initials: H
authors.lastname: Zhou
authors.affiliation: Department of Physiology, Medical College of Georgia at Georgia Regents University, Augusta, Georgia, United States of America.
authors.forename: Siyang
authors.initials: S
authors.lastname: Liu
authors.affiliation: Department of Chemistry, Michigan State University, East Lansing, Michigan, United States of America.
authors.forename: Cassie J
authors.initials: CJ
authors.lastname: Fhaner
authors.affiliation: Department of Chemistry, Michigan State University, East Lansing, Michigan, United States of America.
authors.forename: Bethany C
authors.initials: BC
authors.lastname: Gross
authors.affiliation: Department of Chemistry, Michigan State University, East Lansing, Michigan, United States of America.
authors.forename: Todd A
authors.initials: TA
authors.lastname: Lydic
authors.affiliation: Department of Chemistry, Michigan State University, East Lansing, Michigan, United States of America ; Department of Biochemistry and Molecular Biology, Michigan State University, East Lansing, Michigan, United States of America.
authors.forename: Gavin E
authors.initials: GE
authors.lastname: Reid
mesh_terms: D017667:Adipocytes / Q000378:metabolism*; D050156:Adipogenesis / Q000235:genetics*; D052436:Adipose Tissue, White / Q000378:metabolism*; D000818:Animals; D002454:Cell Differentiation / Q000235:genetics; D044388:GTP-Binding Protein gamma Subunits; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D020962:Heterotrimeric GTP-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D006706:Homeostasis / Q000235:genetics; D050356:Lipid Metabolism / Q000235:genetics*; D008066:Lipolysis / Q000235:genetics; D008297:Male; D051379:Mice; D018345:Mice, Knockout
chemical_list: C115783:Bscl2 protein, mouse; D044388:GTP-Binding Protein gamma Subunits; D020962:Heterotrimeric GTP-Binding Proteins