|ZFIN ID: ZDB-PUB-100910-33|
Zebrafish fat-free, a novel Arf effector, regulates phospholipase D to mediate lipid and glucose metabolism
Liu, H.Y., Lee, N., Tsai, T.Y., and Ho, S.Y.
|Source:||Biochimica et biophysica acta. Molecular and cell biology of lipids 1801(12): 1330-1340 (Journal)|
|Registered Authors:||Ho, Shiu-Ying, Lee, Nancy, Liu, Hsing-Yin|
|Keywords:||fat-free gene, ADP-ribosylation factor, Phospholipase D, Zebrafish, Lipid metabolism, Glucose metabolism|
|PubMed:||20816853 Full text @ BBA Molecular and Cell Biology of Lipids|
Liu, H.Y., Lee, N., Tsai, T.Y., and Ho, S.Y. (2010) Zebrafish fat-free, a novel Arf effector, regulates phospholipase D to mediate lipid and glucose metabolism. Biochimica et biophysica acta. Molecular and cell biology of lipids. 1801(12):1330-1340.
ABSTRACTZebrafish fat-free mutants (ffr) exhibit defective intestinal lipid metabolism and fat-free protein (Ffr) is involved in Golgi-related vesicular trafficking. In this study, we show that ffr mutants also display defective glucose metabolism. Using microarray and real-time PCR, we found that a ffr mutant with a nonsense mutation exhibits increased transcript level of ADP-ribosylation factor gene (arfs). Further analysis indicated Ffr contains a putative Arf binding motif and can bind GTP-bound Arfs. In addition, ffr exhibited increased transcript and activity levels of the Arf downstream effector phospholipase D (PLD). Inhibition of PLD partially restored lipid and glucose metabolism in ffr, suggesting that Ffr is involved in a pathway regulating PLD activity by regulating Arfs. We propose that local over-production of phosphatidic acid (PA) by excess PLD promotes membrane curvature, which affects Golgi membrane structure and secretory processes, contributing to impairment of lipid and glucose metabolism.