Mol Endocrinol 2008,
Chakrabarti, Partha; Anno, Takatoshi; Manning, Brendan D; Luo, Zhijun; Kandror, Konstantin V
Leptin production by adipose cells in vivo is increased after feeding and decreased by food deprivation. However, molecular mechanisms that control leptin expression in response to food intake remain unknown. Here, we test the hypothesis that leptin expression in adipose cells is regulated by nutrient- and insulin-sensitive mammalian target of rapamycin complex 1 (mTORC1)-mediated pathway. The activity of mTORC1 in 3T3-L1 adipocytes was up-regulated by stable expression of either constitutively active Rheb or dominant-negative AMP-activated protein kinase. In both cases, expression of endogenous leptin was significantly elevated at the level of translation. To investigate the role of leptin 5'-untranslated region (UTR) in the regulation of protein expression, we created bicistronic reporter constructs with and without the 5'-UTR. We found that the presence of leptin 5'-UTR renders mRNA resistant to regulation by mTORC1. It appears, therefore, that mTORC1 controls translation of leptin mRNA via a novel mechanism that does not require the presence of either the 5'-terminal oligopyrimidine tract or the 5'-UTR.
Document information provided by NCBI PubMed
Text Mining Data
mTORC1 → Rheb: " The activity of mTORC1
in 3T3-L1 adipocytes was up-regulated
by stable expression of either constitutively active Rheb
or dominant negative AMP activated protein kinase "
Manually curated Databases
No curated data.