CGI-58/ABHD5-Derived Signaling Lipids Regulate Systemic Inflammation and Insulin Action

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FIG. 3.
FIG. 3.

CGI-58–generated signaling lipids are necessary for maximal TNFα signaling in the liver. AC: Mice were maintained on a chow diet for 4 weeks in conjunction with biweekly injections (25 mg/kg) of either a nontargeting control ASO (□) or ASO targeting knockdown of CGI-58 (CGI-58 ASO; ■). Mice were fasted for 10 h before injection of saline or TNFα (10 ng) into the portal vein. Exactly 5 min later, the liver was excised and immediately snap-frozen in liquid nitrogen for signaling analyses. A: Hepatic levels of PA and phosphatidylglycerol (PG) were analyzed by mass spectrometry. B: Total hepatic LPAAT activity. Data in A and B represent the mean ± SEM from four mice per group, and values not sharing a common superscript letter differ significantly (P < 0.05). C: Protein extracts from the liver were analyzed for total IκB α (IκBα) and phospho-IκBα (p-IκBα; Ser32); data from four representative animals are shown for each group. D–F: Acute stress kinase activation in primary hepatocytes. Following 4 weeks of ASO treatment, hepatocytes were isolated from control and CGI-58 ASO-treated mice by collagenase perfusion. Freshly isolated hepatocytes were stimulated for 15 min (15’) or 1 h with 100 ng/mL TNFα (D), 10 ng/mL IL-1β (E), or 10 ng/mL IL-6 (F). Downstream signaling was analyzed by immunoblotting for p-JNK (Thr183/Tyr185), phospho-S6 ribosomal protein (p-S6; Ser235/236), and β-actin. Data in D–F represent responses of hepatocytes isolated from three individual mice per condition.

This Article

  1. Diabetes vol. 61 no. 2 355-363