title: Disabled-2 Determines Commitment of a Pre-adipocyte Population in Juvenile Mice.
abstract: Disabled-2 (Dab2) is a widely expressed clathrin binding endocytic adaptor protein and known for the endocytosis of the low-density lipoprotein (LDL) family receptors. Dab2 also modulates endosomal Ras/MAPK (Erk1/2) activity by regulating the disassembly of Grb2/Sos1 complexes associated with clathrin-coated vesicles. We found that the most prominent phenotype of Dab2 knockout mice was their striking lean body composition under a high fat and high caloric diet, although the weight of the mutant mice was indistinguishable from wild-type littermates on a regular chow. The remarkable difference in resistance to high caloric diet-induced weight gain of the dab2-deleted mice was presented only in juvenile but not in mature mice. Investigation using Dab2-deficient embryonic fibroblasts and mesenchymal stromal cells indicated that Dab2 promoted adipogenic differentiation by modulation of MAPK (Erk1/2) activity, which otherwise suppresses adipogenesis through the phosphorylation of PPARγ. The results suggest that Dab2 is required for the excessive calorie-induced differentiation of an adipocyte progenitor cell population that is present in juvenile but depleted in mature animals. The finding provides evidence for a limited pre-adipocyte population in juvenile mammals and the requirement of Dab2 in the regulation of Ras/MAPK signal in the commitment of the precursor cells to adipose tissues.
authors: Department of Cell Biology and Sylvester Comprehensive Cancer Center, University of Miami Miller School of Medicine, Miami, FL, 33136, USA.|Graduate Program in Molecular Cell and Developmental Biology, University of Miami Miller School of Medicine, Miami, FL 33136 USA.
authors: Wensi
authors: W
authors: Tao
authors: Department of Cell Biology and Sylvester Comprehensive Cancer Center, University of Miami Miller School of Medicine, Miami, FL, 33136, USA.
authors: Robert
authors: R
authors: Moore
authors: Department of Cell Biology and Sylvester Comprehensive Cancer Center, University of Miami Miller School of Medicine, Miami, FL, 33136, USA.|Graduate Program in Molecular Cell and Developmental Biology, University of Miami Miller School of Medicine, Miami, FL 33136 USA.
authors: Yue
authors: Y
authors: Meng
authors: Department of Cell Biology and Sylvester Comprehensive Cancer Center, University of Miami Miller School of Medicine, Miami, FL, 33136, USA.
authors: Toni M
authors: TM
authors: Yeasky
authors: Department of Cell Biology and Sylvester Comprehensive Cancer Center, University of Miami Miller School of Medicine, Miami, FL, 33136, USA.
authors: Elizabeth R
authors: ER
authors: Smith
authors: Department of Cell Biology and Sylvester Comprehensive Cancer Center, University of Miami Miller School of Medicine, Miami, FL, 33136, USA.|Graduate Program in Molecular Cell and Developmental Biology, University of Miami Miller School of Medicine, Miami, FL 33136 USA.
authors: Xiang-Xi
authors: XX
authors: Xu
mesh_terms: D048868:Adaptor Proteins, Signal Transducing; D033942:Adaptor Proteins, Vesicular Transport / Q000172:deficiency / Q000378:metabolism*; D017667:Adipocytes / Q000502:physiology*; D000818:Animals; D051017:Apoptosis Regulatory Proteins; D001835:Body Weight; D002454:Cell Differentiation; D002478:Cells, Cultured; D059305:Diet, High-Fat; D005347:Fibroblasts / Q000502:physiology*; D005786:Gene Expression Regulation; D020935:MAP Kinase Signaling System; D059630:Mesenchymal Stem Cells / Q000502:physiology*; D018345:Mice, Knockout
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D033942:Adaptor Proteins, Vesicular Transport; D051017:Apoptosis Regulatory Proteins; C478773:Dab2 protein, mouse