title: A heterogeneous lineage origin underlies the phenotypic and molecular differences of white and beige adipocytes.
abstract: A worldwide epidemic of obesity and its associated metabolic disorders raise the significance of adipocytes, their origins and characteristics. Our previous study has demonstrated that interscapular brown adipose tissue (BAT), but not intramuscular adipose, is derived from the Pax3-expressing cell lineage. Here, we show that various depots of subcutaneous (SAT) and visceral adipose tissue (VAT) are highly heterogeneous in the Pax3 lineage origin. Interestingly, the relative abundance of Pax3 lineage cells in SAT depots is inversely correlated to expression of BAT signature genes including Prdm16, Pgc1a (Ppargc1a) and Ucp1. FACS analysis further demonstrates that adipocytes differentiated from non-Pax3 lineage preadipocytes express higher levels of BAT and beige adipocyte signature genes compared with the Pax3 lineage adipocytes within the same depots. Although both Pax3 and non-Pax3 lineage preadipocytes can give rise to beige adipocytes, the latter contributes more significantly. Consistently, genetic ablation of Pax3 lineage cells in SAT leads to increased expression of beige cell markers. Finally, non-Pax3 lineage beige adipocytes are more responsive to cAMP-agonist-induced Ucp1 expression. Taken together, these results demonstrate widespread heterogeneity in Pax3 lineage origin, and its inverse association with BAT gene expression within and among subcutaneous adipose depots.
authors.affiliation: Department of Animal Sciences, Purdue University, West Lafayette, IN 47907, USA.
authors.forename: Weiyi
authors.initials: W
authors.lastname: Liu
authors.forename: Tizhong
authors.initials: T
authors.lastname: Shan
authors.forename: Xin
authors.initials: X
authors.lastname: Yang
authors.forename: Sandra
authors.initials: S
authors.lastname: Liang
authors.forename: Pengpeng
authors.initials: P
authors.lastname: Zhang
authors.forename: Yaqin
authors.initials: Y
authors.lastname: Liu
authors.forename: Xiaoqi
authors.initials: X
authors.lastname: Liu
authors.forename: Shihuan
authors.initials: S
authors.lastname: Kuang
mesh_terms: D002001:Adipose Tissue, Brown / Q000166:cytology / Q000378:metabolism / Q000502:physiology*; D052436:Adipose Tissue, White / Q000166:cytology / Q000378:metabolism / Q000502:physiology*; D000818:Animals; D019070:Cell Lineage; D015870:Gene Expression; D005838:Genotype; D051379:Mice; D008822:Mice, Transgenic; D000072041:PAX3 Transcription Factor; D051761:Paired Box Transcription Factors / Q000235:genetics / Q000378:metabolism; D010641:Phenotype; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism
chemical_list: D000072041:PAX3 Transcription Factor; C489409:PAX3 protein, human; D051761:Paired Box Transcription Factors; D014157:Transcription Factors; C068686:Pax3 protein, mouse
keywords: Adipose tissue; Beige adipocyte; Lineage tracing; Pax3