Accelerated essential fatty acid deficiency by delta 9 desaturase induction: dissociation between the effects on liver and other tissues.
Essential fatty acid (EFA) deficiency is an important tool in probing the role of arachidonic acid (20:4(n-6] in pathophysiologic processes, but requires stringent and prolonged deprivation of (n-6) fatty acids. The present study investigated whether induction of the delta 9 desaturase, which is responsible for the synthesis of oleate, the precursor of 20:3(n-9) which uniquely accumulates in the deficiency state, might serve to accelerate the biochemical and biological effects of EFA deficiency. By alternately fasting and feeding animals a fat-free diet, it was possible to induce markedly the delta 9 desaturase selectively in liver. This dietary manipulation in consequence led to dramatic and rapid changes in hepatic phospholipid fatty acid composition. Within 2 weeks, 20:3(n-9) to 20:4(n-6) ratios in liver phospholipids were several fold greater than those seen in animals fed a fat-free diet alone. These changes, however, contrasted with those seen in the serum and other tissues. The mol% of 20:3(n-9) in serum was not increased by delta 9 desaturase induction and the 20:3(n-9) to 20:4(n-6) ratio was only modestly increased. The effects of delta 9 desaturase induction were even more attenuated in tissues other than the liver. Desaturase induction led to a doubling in the 20:3(n-9) to 20:4(n-6) ratio in phosphatidylcholine in renal cortex and heart, although the ratio in the other phospholipids was unaffected. The 20:3(n-9) to 20:4(n-6) ratio in peritoneal macrophage phospholipids was unaffected by desaturase induction. Thus, delta 9 desaturase induction greatly augments the synthesis of (n-9) fatty acids within the liver and leads to the rapid and substantial accumulation of the abnormal fatty acid, 20:3(n-9). This markedly augmented synthesis of hepatic 20:3(n-9), however, is not reflected in increased plasma levels of 20:3(n-9), and thus the effects of delta 9 desaturase induction are attenuated in tissues other than the liver. These data underscore the notable ability of the liver to maintain polyunsaturated fatty acid homeostasis.
Lefkowith
J B
JB
Department of Medicine, Washington University School of Medicine, St. Louis, MO 63110.
D000818:Animals; D001095:Arachidonic Acids / Q000097:blood / Q000378:metabolism; D004032:Diet; D004790:Enzyme Induction; D044943:Fatty Acid Desaturases / Q000096:biosynthesis*; D005228:Fatty Acids, Essential / Q000097:blood / Q000172:deficiency*; D005231:Fatty Acids, Unsaturated; D008099:Liver / Q000201:enzymology / Q000378:metabolism*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009928:Organ Specificity; D010743:Phospholipids / Q000097:blood / Q000378:metabolism; D013230:Stearoyl-CoA Desaturase
D001095:Arachidonic Acids; D005228:Fatty Acids, Essential; D005231:Fatty Acids, Unsaturated; D010743:Phospholipids; D044943:Fatty Acid Desaturases; D013230:Stearoyl-CoA Desaturase; C029627:delta-9 fatty acid desaturase