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. Author manuscript; available in PMC: 2010 Aug 7.
Published in final edited form as: Cell. 2009 Jul 30;138(3):476–488. doi: 10.1016/j.cell.2009.05.036

Figure 7. Portal Vein Infusion of 16:0/18:1-GPC Rescues Hepatic Steatosis in a PPARα-dependent manner.

Figure 7

(A) Operative field depicting the portal vein (PV) cannulated with a catheter (pv-cath) positioned at the entry site into the liver (lvr). The catheter is intentionally marked in black ink at its proximal tip to enhance visualization. Labels indicate gall bladder (gb), bile duct (bd), inferior vena cava (ivc), and pancreas (pan).

(B) Intraportal 16:0/18:1-GPC treatment protocol. After insertion of the portal vein catheter, C57BL/6 mice (wild type for FAS and either wild type or null for PPARα) were allowed to recover. On day 4, chow was changed to a zero fat diet (ZFD) and the mice received 3 intraportal injections/day of 10 mg/kg 16:0/18:1-GPC sonicated in normal saline/0.5% ethanol/0.5% fatty acid-free BSA or vehicle alone. On the last day before the end of treatment (day 9), mice were fasted for 24 h.

(C) At the end of the treatment protocol, liver histological sections were stained with oil red O to visualize neutral lipids (x40 magnification) from wild type (C57/BL6) and PPARα−/− mice treated with 16:0/18:1-GPC or vehicle (Veh). Sections are representative of several animals for each condition.

(D) Quantification of hepatic triglyceride content per unit mass of tissue from vehicle and 16:0/18:1-GPC treated C57/BL6 and PPARα−/− mice. Bars represent mean ± SEM of two separate infusion experiments with 5–8 animals per group in each experiment. *, P < 0.05 vs. corresponding Veh. #, P < 0.05 vs. C57/BL6 controls.

(E) Expression of hepatic ACO (top panel) and CPT-1 (bottom panel) mRNA by RT-PCR normalized to control L32 ribosomal mRNA following the 16:0/18:1-GPC injections. Data represent mean ± SEM of two independent RT-PCR experiments for each gene with 4 mice per genotype per group. *, P < 0.05 vs. corresponding Veh. #, P < 0.05 vs. C57/BL6 controls. (F) Proposed model for the generation of the endogenous PPARα ligand in liver. FAS yields palmitate (C16:0), and 16:0/18:1-GPC is likely generated through the diacylglycerol (DAG) intermediate and the enzymatic activity of CEPT1 either in the ER or the nucleus. Binding of 16:0/18:1-GPC to PPARα in the nucleus activates transcription machinery (TM) turning on PPARα-dependent genes and affecting hepatic lipid metabolism. ACC, acetyl CoA carboxylase; ER, endoplasmic reticulum.