Fructose and glucose can regulate mammalian target of rapamycin complex 1 and lipogenic gene expression via distinct pathways

J Biol Chem. 2018 Feb 9;293(6):2006-2014. doi: 10.1074/jbc.M117.782557. Epub 2017 Dec 8.


Although calorically equivalent to glucose, fructose appears to be more lipogenic, promoting dyslipidemia, fatty liver disease, cardiovascular disease, and diabetes. To better understand how fructose induces lipogenesis, we compared the effects of fructose and glucose on mammalian target of rapamycin complex 1 (mTORC1), which appeared to have both positive and negative effects on lipogenic gene expression. We found that fructose acutely and transiently suppressed mTORC1 signaling in vitro and in vivo The constitutive activation of mTORC1 reduced hepatic lipogenic gene expression and produced hypotriglyceridemia after 1 week of fructose feeding. In contrast, glucose did not suppress mTORC1, and the constitutive activation of mTORC1 failed to suppress plasma triglycerides after 1 week of glucose feeding. Thus, these data reveal fundamental differences in the signaling pathways used by fructose and glucose to regulate lipid metabolism.

Keywords: dyslipidemia; fructose; glucose; lipogenesis; mammalian target of rapamycin (mTOR); metabolic syndrome.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Fructose / metabolism*
  • Gene Expression Regulation*
  • Glucose / metabolism*
  • Lipogenesis*
  • Liver / metabolism
  • Male
  • Mechanistic Target of Rapamycin Complex 1 / genetics*
  • Mechanistic Target of Rapamycin Complex 1 / metabolism
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Signal Transduction
  • Triglycerides / metabolism


  • Triglycerides
  • Fructose
  • Mechanistic Target of Rapamycin Complex 1
  • Glucose