umu.sePublications
Change search
CiteExportLink to record
Permanent link

Direct link
Cite
Citation style
  • apa
  • ieee
  • modern-language-association-8th-edition
  • vancouver
  • Other style
More styles
Language
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Other locale
More languages
Output format
  • html
  • text
  • asciidoc
  • rtf
Lipoprotein lipase: mechanism for adaptation of activity to the nutritional state
Umeå University, Faculty of Medicine, Department of Medical Biosciences, Physiological chemistry.
2004 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

Lipoprotein lipase (LPL) is an enzyme to hydrolyze triglycerides in lipoproteins and thereby make the fatty acids available for cellular metabolic reactions. Short-term fasting down-regulates LPL activity in adipose tissue. This regulation is through post-translational mechanism. The objective of this work was to investigate (1) The molecular mechansim for regulation of LPL activity in adipose tissue; (2) The basis for the tissue-specific regulation of LPL in adipose tissue, heart and skeletal muscle. LPL in adipose tissue can be found both inside (intracellular) and outside adipocytes (extracellular). Within adipocytes, neither LPL mass nor the distribution of LPL between active and inactive forms changed on fasting. Extracellular LPL mass also did not change significantly, but shifted from predominantly active to predominantly inactive. Activie, extracellular LPL was distributed in a similar way in the two nutritional states. The down-regulation during fasting is due to a decline of extracellular LPL activity. The up-regulation of LPL activity induced by re-feeding did not need new mRNA. The down-regulation of LPL activity induced by fasting did not occur when mRNA synthesis was inhibited. LPL activity in adipose tissue from fasted rats was fully restored by actinomycin. So fasting switches on a gene, whose product suppresses LPL activity. Similar results were also obtained in experiments on mice. When food was removed from young rats in the early morning, adipose tissue TNF-α activity increased and LPL activity decreased within six hours. There was a negative correlation between TNF-α and LPL activities. Pentoxifylline, that inhibits biosynthesis of TNF-α, almost abolished the rise of TNF-α and the decrease of LPL activity. Actinomycin D virtually abolished the response of LPL activity to fasting or exogenous TNF-α. This study suggests that fasting signals via TNF-α to a gene whose product causes a rapid shift of newly-synthesized LPL molecules towards an inactive form.

Place, publisher, year, edition, pages
Umeå: Umeå university , 2004. , 60 p.
Series
Umeå University medical dissertations, ISSN 0346-6612 ; 866
Keyword [en]
Biochemistry, adipose tissue, heparin, extracellular, nutrition, turnover, actinomycin
Keyword [sv]
Biokemi
National Category
Biochemistry and Molecular Biology
Research subject
Biochemistry
Identifiers
URN: urn:nbn:se:umu:diva-175ISBN: 91-7305-554-9 (print)OAI: oai:DiVA.org:umu-175DiVA: diva2:141923
Public defence
2004-01-30, N350, NVH-huset, campus, Umeå, 13:00 (English)
Opponent
Supervisors
Available from: 2003-12-23 Created: 2003-12-23 Last updated: 2010-08-27Bibliographically approved
List of papers
1. The distribution of lipoprotein lipase in rat adipose tissue: changes with nutritional state engage the extracellular enzyme
Open this publication in new window or tab >>The distribution of lipoprotein lipase in rat adipose tissue: changes with nutritional state engage the extracellular enzyme
2003 (English)In: Journal of Biological Chemistry, ISSN 0021-9258, E-ISSN 1083-351X, Vol. 278, 11925-11930 p.Article in journal (Refereed) Published
Identifiers
urn:nbn:se:umu:diva-3312 (URN)
Available from: 2003-12-23 Created: 2003-12-23 Last updated: 2017-12-14Bibliographically approved
2. Down-regulation of adipose tissue lipoprotein lipase during fasting requires that a gene, separate from the lipase gene, is switched on
Open this publication in new window or tab >>Down-regulation of adipose tissue lipoprotein lipase during fasting requires that a gene, separate from the lipase gene, is switched on
2002 (English)In: Journal of Biological Chemistry, ISSN 0021-9258, E-ISSN 1083-351X, Vol. 277, 11927-11932 p.Article in journal (Refereed) Published
Identifiers
urn:nbn:se:umu:diva-3313 (URN)
Available from: 2003-12-23 Created: 2003-12-23 Last updated: 2017-12-14Bibliographically approved
3. Rapid downregulation of adipose tissue lipoprotein lipase activity on food deprivation: evidence that TNF-alpha is involved.
Open this publication in new window or tab >>Rapid downregulation of adipose tissue lipoprotein lipase activity on food deprivation: evidence that TNF-alpha is involved.
2004 (English)In: Am J Physiol Endocrinol Metab, ISSN 0193-1849, Vol. 286, no 5, E711-7 p.Article in journal (Refereed) Published
Keyword
Adipose Tissue/drug effects/*enzymology, Animals, Down-Regulation, Food Deprivation/*physiology, Lipopolysaccharides/pharmacology, Lipoprotein Lipase/drug effects/*metabolism, Male, Rats, Rats; Sprague-Dawley, Signal Transduction, Tumor Necrosis Factor-alpha/drug effects/*physiology
Identifiers
urn:nbn:se:umu:diva-15204 (URN)14693508 (PubMedID)
Available from: 2008-01-11 Created: 2008-01-11 Last updated: 2011-01-12Bibliographically approved
4. Nutritional regulation of lipoprotein lipase in mice
Open this publication in new window or tab >>Nutritional regulation of lipoprotein lipase in mice
2004 (English)In: International Journal of Biochemistry and Cell Biology, ISSN 1357-2725, E-ISSN 1878-5875, Vol. 36, no 2, 320-329 p.Article in journal (Refereed) Published
Abstract [en]

Tissue-specific regulation of lipoprotein lipase (LPL) has been extensively studied in rats. The mouse is now the most used animal in lipoprotein research, and we have therefore explored the regulation of LPL in this species. In C57 black mice, fed ad libitum adipose tissue LPL activity changed about three-fold with the time of day, indicating a circadian rhythm. The highest activity was at midnight and the lowest activity was at noon. Withdrawal of food did not markedly accelerate the drop of activity that occurred from midnight until noon, but prevented the return of activity that occurred during the evening and early night. When food was returned to mice that had been fasted for 24h, adipose tissue LPL activity rose rapidly and returned to the fed level in 2h. LPL mass in adipose tissue changed less than LPL activity, indicating that regulation is mainly post-translational as previously demonstrated for rats. When transcription was blocked in fasted mice, adipose tissue LPL activity increased, as previously observed in rats. LPL activity in heart was highest early in the light period at 9:00h and lowest at 21:00h. The change was, however, only about 30%. Heparin-releasable LPL activity in heart was 1.8-fold higher in mice fasted for 6h compared to fed controls. We conclude that LPL activity responds to the nutritional state in the same direction and by the same mechanisms in mice as in rats, but the magnitude of the changes are less in mice.

Keyword
Adipose Tissue/metabolism, Animal Nutrition Physiology, Animals, Circadian Rhythm, Dactinomycin/pharmacology, Food Deprivation, Lipoprotein Lipase/*biosynthesis/metabolism, Male, Mice, Mice; Inbred C57BL, Myocardium/metabolism, Time Factors, Transcription; Genetic
Identifiers
urn:nbn:se:umu:diva-15202 (URN)10.1016/S1357-2725(03)00256-5 (DOI)14643896 (PubMedID)
Available from: 2008-01-11 Created: 2008-01-11 Last updated: 2017-12-14Bibliographically approved

Open Access in DiVA

fulltext(241 kB)1011 downloads
File information
File name FULLTEXT01.pdfFile size 241 kBChecksum SHA-1
4d3ac9caf01bd2f2f21c47412481d70a6714f548d9759395114dae0244d81dc1adf5cae7
Type fulltextMimetype application/pdf

By organisation
Physiological chemistry
Biochemistry and Molecular Biology

Search outside of DiVA

GoogleGoogle Scholar
Total: 1011 downloads
The number of downloads is the sum of all downloads of full texts. It may include eg previous versions that are now no longer available

isbn
urn-nbn

Altmetric score

isbn
urn-nbn
Total: 734 hits
CiteExportLink to record
Permanent link

Direct link
Cite
Citation style
  • apa
  • ieee
  • modern-language-association-8th-edition
  • vancouver
  • Other style
More styles
Language
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Other locale
More languages
Output format
  • html
  • text
  • asciidoc
  • rtf