Role of Gas-6 in adipogenesis and nutritionally induced adipose tissue development in mice.
OBJECTIVE
A potential role of growth arrest-specific gene 6 (Gas-6) in energy storage in adipose tissue was investigated in murine models of obesity. Gas-6 is a ligand for the Axl, C-Mer, and Sky family of tyrosine kinase receptors.


RESULTS
Whereas Gas-6, C-Mer, and Sky were expressed in mature murine adipocytes, the expression of Axl was restricted to the stromal-vascular fraction, which includes pre-adipocytes. During the in vitro conversion of adipogenic 3T3-F442A cells into mature adipocytes, the expression of Gas-6 increased in undifferentiated confluent pre-adipocytes during a transient phase of growth arrest. On treatment of these cells with an adipogenic medium, Gas-6 expression decreased sharply, coinciding with expression of early adipocytes markers. This modulation was not observed in the nonadipogenic 3T3-C2 cells. The Gas-6 mRNA level was transiently downregulated during nutritionally induced expansion of adipose tissues in vivo. When kept on a standard diet, no significant difference in either total body weight or weight of gonadal or subcutaneous fat pads was observed between Gas-6 deficient and wild-type mice. On exposure to a high-fat diet, however, Gas-6-deficient mice had significantly less fat mass than their wild-type counterparts.


CONCLUSIONS
Gas-6 enhances the accumulation of adipose tissue in diet-induced obese mice.
Maquoi
Erik
E
Center for Molecular and Vascular Biology, KU Leuven, Leuven, Belgium.
Vörös
Gabor
G
Carmeliet
Peter
P
Collen
Désiré
D
Lijnen
H Roger
HR
D016475:3T3 Cells; D017667:Adipocytes / Q000166:cytology / Q000502:physiology; D050156:Adipogenesis / Q000502:physiology*; D000273:Adipose Tissue / Q000166:cytology / Q000473:pathology / Q000502:physiology*; D000824:Animal Nutritional Physiological Phenomena; D000818:Animals; D002454:Cell Differentiation / Q000502:physiology; D004041:Dietary Fats / Q000494:pharmacology; D004195:Disease Models, Animal; D015870:Gene Expression; D036341:Intercellular Signaling Peptides and Proteins / Q000235:genetics* / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D008817:Mice, Mutant Strains; D009765:Obesity / Q000235:genetics / Q000473:pathology / Q000503:physiopathology*; D015513:Oncogene Proteins / Q000235:genetics; D011518:Proto-Oncogene Proteins / Q000235:genetics; D020794:Receptor Protein-Tyrosine Kinases / Q000235:genetics; D000076202:c-Mer Tyrosine Kinase; D000094963:Axl Receptor Tyrosine Kinase; D000099255:Growth Arrest-Specific Protein 6
D004041:Dietary Fats; D036341:Intercellular Signaling Peptides and Proteins; D015513:Oncogene Proteins; D011518:Proto-Oncogene Proteins; D020794:Receptor Protein-Tyrosine Kinases; D000076202:c-Mer Tyrosine Kinase; D000094963:Axl Receptor Tyrosine Kinase; D000099255:Growth Arrest-Specific Protein 6; C490767:Mertk protein, mouse; C000722290:AXL receptor tyrosine kinase, mouse