Ras Proteins Mediate Induction of Uncoupling Protein, IGF-I, and IGF-I Receptor in Rat Fetal Brown Adipocyte Cell Lines

摘要

ABSTRACTSince Ras proteins are essential intermediates of some insulin-like growth factor I (IGF-I)/insulin signaling pathways, we examined whether Ras proteins mediate the IGF-I-induced uncoupling protein expression. Additionally, the role of Ras proteins on IGF-I and IGF-I receptor expression was studied. IGF-I treatment of fetal brown adipocytes cotransfected with inducible gene constructs of SV40 large T antigen (SV40LTag) and a transformingrasgene induced uncoupling protein expression (UCP) in the absence of expression of the transfected genes. The expression of the dexamethasone-inducible transformingrasgene alone or in combination with the Zn-inducible SV40LTag mimicked the IGF-I effect inducing UCP expression and IGF-I did not induce it further. However, the expression of the Zn-inducible SV40LTag did not increase UCP expression in the absence of IGF-I. Expression of the transfectedrasoncogene also induced IGF-I and IGF-I receptor mRNAs, whereas expression of SV40LTag did not increase them. Specific IGF-I binding was also specifically increased by expression of the transfectedrasoncogene but was not affected by expression of the SV40LTag construct. These results indicate that Ras proteins mediate the IGF-I-induced effect on UCP expression and play a role in the expression of IGF-I and IGF-I receptor. Therefore, an IGF-I autocrine/paracrine loop might be implicated in the process of thermogenic differentiation of brown adipose tissue by a new mechanism unlike that induced by norepinephrine.