title: The response of lipoprotein lipase to feeding and fasting. Evidence for posttranslational regulation.
abstract: 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.
authors.affiliation: Veterans Administration Wadsworth Medical Center, Los Angeles, California 90073.
authors.forename: M H
authors.initials: MH
authors.lastname: Doolittle
authors.forename: O
authors.initials: O
authors.lastname: Ben-Zeev
authors.forename: J
authors.initials: J
authors.lastname: Elovson
authors.forename: D
authors.initials: D
authors.lastname: Martin
authors.forename: T G
authors.initials: TG
authors.lastname: Kirchgessner
mesh_terms: 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
chemical_list: D012333:RNA, Messenger; D008071:Lipoprotein Lipase; D006596:Hexosaminidases; D008358:Mannose