Effects of arachidonic and docosahexaenoic acids on secretion and degradation of bile salt-dependent lipase in AR4-2J cells

In this study we demonstrated that two polyunsat- urated fatty acids, arachidonic acid (AA, n-6) and docosa- hexaenoic acid (DHA, n-3), modulate the secretion of bile salt-dependent lipase (BSDL) by pancreatic AR4-2J cells. The effects of AA and DHA were also compared with that of the monounsaturated fatty acid, oleic acid (OA). Our re- sults showed that the chronic treatment of cells with AA or DHA, that did not affect the biosynthesis rate of BSDL, sim- ilarly decreased the amount of secreted BSDL and per- turbed the intracellular partitioning of the enzyme, whereas OA had no effect. Particularly, AA and DHA induced the re- tention of the enzyme in microsomes and lowered its con- tent in the cell cytosol. We have further shown that AA treat- ment decreased the ubiquitination of the protein, and consequently diminished its export toward the cytosol, a re- sult that might explain the retention of BSDL in microsomes and correlated with membrane phospholipids alteration. The retained protein was further degraded by a nonproteasomal pathway that likely involves ATP-dependent endoplasmic reticulum proteases. These findings concerning the regu- lation of the pancreatic BSDL secretion by two polyunsatu- rated acids, AA and DHA, might be of physiological impor- tance in the plasmatic and cellular cholesterol homeostasis. —Le Petit-Thevenin, J., N. Bruneau, A. Nganga, D. Lom- bardo, and A. Verine. Effects of arachidonic and docosa- hexaenoic acids on secretion and degradation of bile salt- dependent lipase in AR4-2J cells. J. Lipid Res. 2001 42: 1220-1230.