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O-GlcNAc: A Bittersweet Switch in Liver.

Zhang K, Yin R, Yang X - Front Endocrinol (Lausanne) (2014)

Bottom Line: The liver is a vital organ responsible for maintaining nutrient homeostasis.These metabolic changes involve spatiotemporally co-ordinated signaling cascades.O-linked β-N-acetylglucosamine (O-GlcNAc) modification has been recognized as a nutrient sensor and regulatory molecular switch.

View Article: PubMed Central - PubMed

Affiliation: Program in Integrative Cell Signaling and Neurobiology of Metabolism, Yale University School of Medicine , New Haven, CT , USA ; Section of Comparative Medicine, Yale University School of Medicine , New Haven, CT , USA ; Department of Cellular and Molecular Physiology, Yale University School of Medicine , New Haven, CT , USA.

ABSTRACT
The liver is a vital organ responsible for maintaining nutrient homeostasis. After a meal, insulin stimulates glycogen and lipid synthesis in the liver; in the fasted state, glucagon induces gluconeogenesis and ketogenesis, which produce glucose and ketone bodies for other tissues to use as energy sources. These metabolic changes involve spatiotemporally co-ordinated signaling cascades. O-linked β-N-acetylglucosamine (O-GlcNAc) modification has been recognized as a nutrient sensor and regulatory molecular switch. This review highlights mechanistic insights into spatiotemporal regulation of liver metabolism by O-GlcNAc modification and discusses its pathophysiological implications in insulin resistance, non-alcoholic fatty liver disease, and fibrosis.

No MeSH data available.


Related in: MedlinePlus

O-GlcNAc regulation of liver disease. Aberrant hepatic O-GlcNAcylation leads to hyperglycemia by attenuating insulin signaling, activating gluconeogenesis, and suppressing glycogen synthesis. O-GlcNAcylation may contribute to NAFLD by stimulating de novo lipogenesis. O-GlcNAcylation may also play a role in the initiation and the progress of fibrosis by activating HSCs. Key targets of O-GlcNAcylation involved in related pathways are listed.
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Figure 3: O-GlcNAc regulation of liver disease. Aberrant hepatic O-GlcNAcylation leads to hyperglycemia by attenuating insulin signaling, activating gluconeogenesis, and suppressing glycogen synthesis. O-GlcNAcylation may contribute to NAFLD by stimulating de novo lipogenesis. O-GlcNAcylation may also play a role in the initiation and the progress of fibrosis by activating HSCs. Key targets of O-GlcNAcylation involved in related pathways are listed.

Mentions: The liver is an insulin-sensitive organ critical for the maintenance of nutrient homeostasis. Hepatic insulin resistance produces derangements in liver metabolism such as uncontrolled glucose production, impaired glycogen synthesis, and enhanced lipogenesis. In the development of hepatic insulin resistance, O-GlcNAcylation is associated with various changes in gluconeogenesis, glycogenesis, and glycolysis. As discussed above, O-GlcNAcylation has been identified as a negative regulator of insulin signal transduction. Hepatic overexpression of OGT in mice impairs the expression of insulin-responsive genes and causes insulin resistance and dyslipidaemia (28, 50) (Figure 3).


O-GlcNAc: A Bittersweet Switch in Liver.

Zhang K, Yin R, Yang X - Front Endocrinol (Lausanne) (2014)

O-GlcNAc regulation of liver disease. Aberrant hepatic O-GlcNAcylation leads to hyperglycemia by attenuating insulin signaling, activating gluconeogenesis, and suppressing glycogen synthesis. O-GlcNAcylation may contribute to NAFLD by stimulating de novo lipogenesis. O-GlcNAcylation may also play a role in the initiation and the progress of fibrosis by activating HSCs. Key targets of O-GlcNAcylation involved in related pathways are listed.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4269194&req=5

Figure 3: O-GlcNAc regulation of liver disease. Aberrant hepatic O-GlcNAcylation leads to hyperglycemia by attenuating insulin signaling, activating gluconeogenesis, and suppressing glycogen synthesis. O-GlcNAcylation may contribute to NAFLD by stimulating de novo lipogenesis. O-GlcNAcylation may also play a role in the initiation and the progress of fibrosis by activating HSCs. Key targets of O-GlcNAcylation involved in related pathways are listed.
Mentions: The liver is an insulin-sensitive organ critical for the maintenance of nutrient homeostasis. Hepatic insulin resistance produces derangements in liver metabolism such as uncontrolled glucose production, impaired glycogen synthesis, and enhanced lipogenesis. In the development of hepatic insulin resistance, O-GlcNAcylation is associated with various changes in gluconeogenesis, glycogenesis, and glycolysis. As discussed above, O-GlcNAcylation has been identified as a negative regulator of insulin signal transduction. Hepatic overexpression of OGT in mice impairs the expression of insulin-responsive genes and causes insulin resistance and dyslipidaemia (28, 50) (Figure 3).

Bottom Line: The liver is a vital organ responsible for maintaining nutrient homeostasis.These metabolic changes involve spatiotemporally co-ordinated signaling cascades.O-linked β-N-acetylglucosamine (O-GlcNAc) modification has been recognized as a nutrient sensor and regulatory molecular switch.

View Article: PubMed Central - PubMed

Affiliation: Program in Integrative Cell Signaling and Neurobiology of Metabolism, Yale University School of Medicine , New Haven, CT , USA ; Section of Comparative Medicine, Yale University School of Medicine , New Haven, CT , USA ; Department of Cellular and Molecular Physiology, Yale University School of Medicine , New Haven, CT , USA.

ABSTRACT
The liver is a vital organ responsible for maintaining nutrient homeostasis. After a meal, insulin stimulates glycogen and lipid synthesis in the liver; in the fasted state, glucagon induces gluconeogenesis and ketogenesis, which produce glucose and ketone bodies for other tissues to use as energy sources. These metabolic changes involve spatiotemporally co-ordinated signaling cascades. O-linked β-N-acetylglucosamine (O-GlcNAc) modification has been recognized as a nutrient sensor and regulatory molecular switch. This review highlights mechanistic insights into spatiotemporal regulation of liver metabolism by O-GlcNAc modification and discusses its pathophysiological implications in insulin resistance, non-alcoholic fatty liver disease, and fibrosis.

No MeSH data available.


Related in: MedlinePlus