The response of lipoprotein lipase to feeding and fasting. Evidence for posttranslational regulation.
The regulation of adipose tissue lipoprotein lipase (LPL) was examined in rats fed or fasted overnight, and was found to be controlled posttranslationally. LPL catalytic activity decreased by 50% after fasting while LPL mRNA levels and rates of synthesis increased nearly 2-fold; enzyme mass remained unchanged. The distribution of LPL within the endoplasmic reticulum (ER) and Golgi/post-Golgi secretory pathway was assessed by differentiating between LPL high mannose and complex forms. After fasting, the majority of LPL is in the high mannose ER form (65%, 0.97 micrograms/g wet weight tissue), whereas the LPL complex form comprises only 35% (or 0.52 micrograms/g). After refeeding, however, the Golgi-derived LPL complex form predominates (65%, 1.03 micrograms/g) over the high mannose ER form (35%, 0.55 micrograms/g). Kinetic analysis suggests that high mannose LPL disappears with a half-life of t0.5 = 40 min in both fed and fasted rats, indicating that the redistribution of LPL mass during feeding/fasting does not arise by differential retention within ER. Instead, the fractional catabolic rate of complex LPL within the Golgi/post-Golgi secretory compartment can be calculated to be 3.5-fold greater in fasting. In heart, changes in LPL activity in response to feeding/fasting are also not due to differences in mRNA levels or rates of synthesis. Based on these findings, a model of LPL posttranslational regulation is proposed and discussed.
Doolittle
M H
MH
Veterans Administration Wadsworth Medical Center, Los Angeles, California 90073.
Ben-Zeev
O
O
Elovson
J
J
Martin
D
D
Kirchgessner
T G
TG
D000273:Adipose Tissue / Q000201:enzymology* / Q000648:ultrastructure; D000595:Amino Acid Sequence; D000818:Animals; D004721:Endoplasmic Reticulum / Q000201:enzymology; D005215:Fasting; D005502:Food; D006031:Glycosylation; D006056:Golgi Apparatus / Q000201:enzymology; D006596:Hexosaminidases / Q000378:metabolism; D007700:Kinetics; D008071:Lipoprotein Lipase / Q000235:genetics / Q000378:metabolism*; D008297:Male; D008358:Mannose / Q000032:analysis; D008969:Molecular Sequence Data; D009206:Myocardium / Q000201:enzymology; D011499:Protein Processing, Post-Translational; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains
D012333:RNA, Messenger; D008071:Lipoprotein Lipase; D006596:Hexosaminidases; D008358:Mannose