Nonreceptor tyrosine phosphatase Shp2 promotes adipogenesis through inhibition of p38 MAP kinase

• DOI: 10.1073/pnas.1213000110
• Publication Date: 2012-12-12T02:28:16Z
• Authors: Zhao He; Helen H. Zhu; Timothy J. Bauler; Jing Wang; Theodore Ciaraldi; Nazilla Alderson; Shuangwei Li; Marie-Astrid Raquil; Kaihong Ji; Shufen Wang; Jianhua Shao; Robert R. Henry; Philip D. King; Gen-Sheng Feng
• Keywords: Leptin; Mice, Knockout; 2. Zero hunger; 0303 health sciences; Adipogenesis; Lipodystrophy; Blood Pressure; Protein Tyrosine Phosphatase, Non-Receptor Type 11; Real-Time Polymerase Chain Reaction; p38 Mitogen-Activated Protein Kinases; 3. Good health; PPAR gamma; Disease Models, Animal; Mice; 03 medical and health sciences; Adipose Tissue; Animals; E1A-Associated p300 Protein; Protein Kinases; Gene Deletion; DNA Primers; Signal Transduction

The molecular mechanism underlying adipogenesis and the physiological functions of adipose tissue are not fully understood. We describe here a unique mouse model severe lipodystrophy. Ablation Ptpn11/Shp2 in adipocytes, mediated by aP2-Cre , led to premature death, lack white fat, low blood pressure, compensatory erythrocytosis, hepatic steatosis Shp2 fat−/− mice. Fat transplantation partially rescued lifespan pressure mice, administration leptin also restored mutant animals with endogenous deficiency. Consistently, homozygous deletion inhibited adipocyte differentiation from embryonic stem (ES) cells. Biochemical analyses suggest Shp2-TAO2-p38-p300-PPARγ pathway adipogenesis, which suppresses p38 activation, leading stabilization p300 enhanced PPARγ expression. Inhibition −/− ES cells, signaling is suppressed obese patients animals. These results illustrate an essential role mammalian survival physiology common involved obesity development.