| CGI-58/ABHD5-Derived Signaling Lipids Regulate Systemic Inflammation and Insulin Action. | |
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MedLine Citation:
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PMID: 22228714 Owner: NLM Status: Publisher |
Abstract/OtherAbstract:
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Mutations of comparative gene identification 58 (CGI-58) in humans cause Chanarin-Dorfman syndrome, a rare autosomal recessive disease in which excess triacylglycerol (TAG) accumulates in multiple tissues. CGI-58 recently has been ascribed two distinct biochemical activities, including coactivation of adipose triglyceride lipase and acylation of lysophosphatidic acid (LPA). It is noteworthy that both the substrate (LPA) and the product (phosphatidic acid) of the LPA acyltransferase reaction are well-known signaling lipids. Therefore, we hypothesized that CGI-58 is involved in generating lipid mediators that regulate TAG metabolism and insulin sensitivity. Here, we show that CGI-58 is required for the generation of signaling lipids in response to inflammatory stimuli and that lipid second messengers generated by CGI-58 play a critical role in maintaining the balance between inflammation and insulin action. Furthermore, we show that CGI-58 is necessary for maximal T(H)1 cytokine signaling in the liver. This novel role for CGI-58 in cytokine signaling may explain why diminished CGI-58 expression causes severe hepatic lipid accumulation yet paradoxically improves hepatic insulin action. Collectively, these findings establish that CGI-58 provides a novel source of signaling lipids. These findings contribute insight into the basic mechanisms linking T(H)1 cytokine signaling to nutrient metabolism. |
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Authors:
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Caleb C Lord; Jenna L Betters; Pavlina T Ivanova; Stephen B Milne; David S Myers; Jennifer Madenspacher; Gwynneth Thomas; Soonkyu Chung; Mingxia Liu; Matthew A Davis; Richard G Lee; Rosanne M Crooke; Mark J Graham; John S Parks; Dawn L Brasaemle; Michael B Fessler; H Alex Brown; J Mark Brown |
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Publication Detail:
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Type: JOURNAL ARTICLE Date: 2012-1-6 |
Journal Detail:
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Title: Diabetes Volume: - ISSN: 1939-327X ISO Abbreviation: - Publication Date: 2012 Jan |
Date Detail:
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Created Date: 2012-1-9 Completed Date: - Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 0372763 Medline TA: Diabetes Country: - |
Other Details:
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Languages: ENG Pagination: - Citation Subset: - |
Affiliation:
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Department of Pathology, Section on Lipid Sciences, Wake Forest University School of Medicine, Winston-Salem, North Carolina. |
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From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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