Submitted on August 2, 2008
Revised on December 25, 2008
Accepted on January 28, 2009
Amino acid-sensing mTOR signaling is involved in modulation of lipolysis by chronic insulin treatment in adipocytes
Chongben Zhang1*, Mee-Sup Yoon2, and Jie Chen2
1 Univ. Ill-Urbana
2 Univ. Ill.-Urbana
* To whom correspondence should be addressed. E-mail: chbzhang{at}uiuc.edu.
Chronically high insulin levels and increased circulating free fatty acids released from adipose tissue through lipolysis are two features associated with insulin resistance. The relationship between chronic insulin exposure and adipocyte lipolysis has been unclear. In the present study we found that chronic insulin exposure in 3T3-L1 adipocytes, as well as in mouse primary adipocytes, increased basal lipolysis rates. This effect of insulin on lipolysis was only observed when the mammalian target of rapamycin (mTOR) pathway was inhibited by rapamycin in the adipocytes. The synergistic effect of insulin and rapamycin was confirmed by the effect of insulin in cells with mTOR levels reduced by RNAi. In addition, amino acid deprivation in adipocytes phenocopied the effect of rapamycin or mTOR knockdown in permitting the stimulation of lipolysis by chronic insulin exposure. Furthermore, we found that triacylglycerol hydrolase (TGH) activity was required for the stimulation of lipolysis by the combined exposure to insulin and rapamycin. Therefore, we propose that nutrient sufficiency, mediated by an mTOR pathway, suppresses TGH-dependent lipolysis stimulated by chronic insulin exposure in adipocytes.
