title: Defective differentiation of adipose precursor cells from lipodystrophic mice lacking perilipin 1.
abstract: Perilipin 1 (Plin1) localizes at the surface of lipid droplets to regulate triglyceride storage and hydrolysis in adipocytes. Plin1 defect leads to low adiposity in mice and partial lipodystrophy in human. This study investigated the roles of Plin1 in adipocyte differentiation. Plin1 null (-/-) mice showed plenty of multilocular adipocytes and small unilocular adipocytes in adipose tissue, along with lack of a subpopulation of adipose progenitor cells capable of in vivo adipogenesis and along with downregulation of adipogenic pathway. Before initiation of differentiation, adipose stromal-vascular cells (SVCs) from Plin1-/- mice already accumulated numerous tiny lipid droplets, which increased in number and size during the first 12-h induction but thereafter became disappeared at day 1 of differentiation. The adipogenic signaling was dysregulated despite protein level of PPARγ was near normal in Plin1-/- SVCs like in Plin1-/- adipose tissue. Heterozygous Plin1+/- SVCs were able to develop lipid droplets, with both the number and size more than in Plin1-/- SVCs but less than in Plin1+/+ SVCs, indicating that Plin1 haploinsufficiency accounts for attenuated adipogenesis. Aberrant lipid droplet growth and differentiation of Plin1-/- SVCs were rescued by adenoviral Plin1 expression and were ameliorated by enhanced or prolonged adipogenic stimulation. Our finding suggests that Plin1 plays an important role in adipocyte differentiation and provides an insight into the pathology of partial lipodystrophy in patients with Plin1 mutation.
authors.affiliation: Department of Physiology and Pathophysiology, School of Basic Medical Sciences, Peking University, Beijing, 100191, China.
authors.forename: Ying
authors.initials: Y
authors.lastname: Lyu
authors.affiliation: Department of Physiology and Pathophysiology, School of Basic Medical Sciences, Peking University, Beijing, 100191, China.
authors.forename: Xueying
authors.initials: X
authors.lastname: Su
authors.affiliation: Department of Physiology and Pathophysiology, School of Basic Medical Sciences, Peking University, Beijing, 100191, China.
authors.forename: Jingna
authors.initials: J
authors.lastname: Deng
authors.affiliation: Department of Physiology and Pathophysiology, School of Basic Medical Sciences, Peking University, Beijing, 100191, China.
authors.forename: Shangxin
authors.initials: S
authors.lastname: Liu
authors.affiliation: Department of Physiology and Pathophysiology, School of Basic Medical Sciences, Peking University, Beijing, 100191, China.
authors.forename: Liangqiang
authors.initials: L
authors.lastname: Zou
authors.affiliation: Department of Physiology and Pathophysiology, School of Basic Medical Sciences, Peking University, Beijing, 100191, China.
authors.forename: Xiaojing
authors.initials: X
authors.lastname: Zhao
authors.affiliation: Department of Physiology and Pathophysiology, School of Basic Medical Sciences, Peking University, Beijing, 100191, China.
authors.forename: Suning
authors.initials: S
authors.lastname: Wei
authors.affiliation: Department of Physiology and Pathophysiology, School of Basic Medical Sciences, Peking University, Beijing, 100191, China.
authors.forename: Bin
authors.initials: B
authors.lastname: Geng
authors.affiliation: Department of Physiology and Pathophysiology, School of Basic Medical Sciences, Peking University, Beijing, 100191, China.
authors.forename: Guoheng
authors.initials: G
authors.lastname: Xu
mesh_terms: D015056:1-Methyl-3-isobutylxanthine / Q000494:pharmacology; D050156:Adipogenesis / Q000187:drug effects; D000273:Adipose Tissue / Q000166:cytology / Q000378:metabolism*; D000818:Animals; D022762:CCAAT-Enhancer-Binding Proteins / Q000235:genetics / Q000378:metabolism; D002352:Carrier Proteins / Q000235:genetics* / Q000378:metabolism*; D050356:Lipid Metabolism / Q000502:physiology; D008060:Lipodystrophy / Q000378:metabolism / Q000473:pathology; D008066:Lipolysis / Q000502:physiology; D051379:Mice; D018345:Mice, Knockout; D008856:Microscopy, Fluorescence; D047495:PPAR gamma / Q000235:genetics / Q000378:metabolism; D000070778:Perilipin-1; D010726:Phosphodiesterase Inhibitors / Q000494:pharmacology; D010750:Phosphoproteins / Q000235:genetics* / Q000378:metabolism*; D015398:Signal Transduction; D013234:Stem Cells / Q000166:cytology / Q000378:metabolism; D051780:Sterol Regulatory Element Binding Protein 1 / Q000235:genetics / Q000378:metabolism
chemical_list: D022762:CCAAT-Enhancer-Binding Proteins; D002352:Carrier Proteins; C000602978:PLIN1 protein, human; D047495:PPAR gamma; D000070778:Perilipin-1; D010726:Phosphodiesterase Inhibitors; D010750:Phosphoproteins; C000602979:Plin1 protein, mouse; C497388:Srebf1 protein, mouse; D051780:Sterol Regulatory Element Binding Protein 1; D015056:1-Methyl-3-isobutylxanthine