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

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

Author information

1
From the Division of Endocrinology, Boston Children's Hospital, Harvard Medical School, Boston, Massachusetts 02115.
2
Division of Endocrinology, Metabolism and Diabetes, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, Massachusetts 02215.
3
INSERM Lipid Nutrition Cancer UMR 1231, 21000 Dijon, France, and.
4
Duke Molecular Physiology Institute and Sarah W. Stedman Nutrition and Metabolism Center, Duke University Medical Center, Durham, North Carolina 27710.
5
From the Division of Endocrinology, Boston Children's Hospital, Harvard Medical School, Boston, Massachusetts 02115, ji.miao@childrens.harvard.edu.
6
From the Division of Endocrinology, Boston Children's Hospital, Harvard Medical School, Boston, Massachusetts 02115, sudha.biddinger@childrens.harvard.edu.

Abstract

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

PMID:
29222328
PMCID:
PMC5808762
DOI:
10.1074/jbc.M117.782557
[Indexed for MEDLINE]
Free PMC Article

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