What question did this study set out to answer?

To determine how CGI-58 knockdown prevents hepatic insulin resistance despite causing severe hepatic steatosis and diacylglycerol accumulation.

January 9, 2013Proceedings of the National Academy of SciencesOpen Access

CGI-58 knockdown sequesters diacylglycerols in lipid droplets/ER-preventing diacylglycerol-mediated hepatic insulin resistance

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To determine how CGI-58 knockdown prevents hepatic insulin resistance despite causing severe hepatic steatosis and diacylglycerol accumulation.
Treated mice with antisense oligonucleotides (ASO) targeting CGI-58 to induce hepatic steatosis.
Assessed systemic and hepatic insulin action using hyperinsulinemic-euglycemic clamp studies.
Fractionated liver cells to analyze the cellular compartmentation of diacylglycerol (DAG) and the activation of protein kinase C epsilon (PKCε).
CGI-58 ASO treatment protected mice against lipid-induced hepatic insulin resistance despite severe hepatic steatosis and elevated total hepatocellular DAG levels.
High-fat diet feeding elevated DAG in cellular membrane fractions, driving PKCε translocation and triggering hepatic insulin resistance.
CGI-58 knockdown redirected DAG accumulation into lipid droplets and the endoplasmic reticulum, preventing PKCε translocation to the plasma membrane and preserving insulin sensitivity.

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Implication

Animal study demonstrates that CGI-58 knockdown traps diacylglycerols in lipid droplets, preventing hepatic insulin resistance and highlighting the role of lipid compartmentalization.

Cite This Study

Cantley et al. (2013) studied this question.

synapsesocial.com/papers/6a77e1ea2e130d02afecd910 https://doi.org/10.1073/pnas.1219456110

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Implication

Animal study demonstrates that CGI-58 knockdown traps diacylglycerols in lipid droplets, preventing hepatic insulin resistance and highlighting the role of lipid compartmentalization.

CGI-58 knockdown sequesters diacylglycerols in lipid droplets/ER-preventing diacylglycerol-mediated hepatic insulin resistance

Key Points

Discussion

Implication

Cite This Study

CGI-58 knockdown sequesters diacylglycerols in lipid droplets/ER-preventing diacylglycerol-mediated hepatic insulin resistance

Key Points

Discussion

Implication

Cite This Study

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