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CGI-58/ABHD5-derived signaling lipids regulate systemic inflammation and insulin action.
Caleb C Lord1, Jenna L Betters, Pavlina T Ivanova
1Department of Pathology, Section on Lipid Sciences, Wake Forest University School of Medicine, Winston-Salem, North Carolina, USA.
Diabetes
|January 10, 2012
Summary
Comparative gene identification 58 (CGI-58) generates signaling lipids crucial for balancing inflammation and insulin action. This finding reveals CGI-58
Area of Science:
- Biochemistry
- Cell Biology
- Metabolic Diseases
Background:
- Mutations in comparative gene identification 58 (CGI-58) cause Chanarin-Dorfman syndrome, characterized by triacylglycerol (TAG) accumulation.
- CGI-58 possesses dual activities: coactivating adipose triglyceride lipase and acylating lysophosphatidic acid (LPA).
- LPA and its product, phosphatidic acid, are recognized signaling lipids, suggesting CGI-58's role in lipid mediator generation.
Purpose of the Study:
- To investigate the hypothesis that CGI-58 generates lipid mediators regulating TAG metabolism and insulin sensitivity.
- To elucidate CGI-58's role in lipid mediator generation during inflammatory responses.
- To determine CGI-58's involvement in TH1 cytokine signaling and its impact on hepatic lipid metabolism and insulin action.
Main Methods:
- Investigated CGI-58's role in signaling lipid generation.
- Assessed the impact of CGI-58 on lipid second messengers.
- Examined CGI-58's necessity for TH1 cytokine signaling in the liver.
Main Results:
- CGI-58 is essential for generating signaling lipids in response to inflammatory stimuli.
- Lipid second messengers produced by CGI-58 are critical for balancing inflammation and insulin action.
- CGI-58 is required for maximal TH1 cytokine signaling in the liver, explaining improved hepatic insulin action despite lipid accumulation.
Conclusions:
- CGI-58 serves as a novel source of signaling lipids.
- CGI-58 plays a critical role in linking TH1 cytokine signaling to nutrient metabolism.
- Understanding CGI-58's function provides insight into lipid metabolism and insulin sensitivity.
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