A transcription-dependent mechanism, akin to that in adipose tissue, modulates lipoprotein lipase activity in rat heart.
The enzyme lipoprotein lipase (LPL) releases fatty acids from lipoprotein triglycerides for use in cell metabolism. LPL activity is rapidly modulated in a tissue-specific manner. Recent studies have shown that in rat adipose tissue this occurs by a shift of extracellular LPL toward an inactive form catalyzed by an LPL-controlling protein whose expression changes in response to the nutritional state. To explore whether a similar mechanism operates in other tissues we injected actinomycin D to block transcription of the putative LPL controlling protein(s). When actinomycin was given to fed rats, heparin-releasable LPL activity increased by 160% in heart and by 150% in a skeletal muscle (soleus) in 6 h. Postheparin LPL activity in blood increased by about 200%. To assess the state of extracellular LPL we subjected the spontaneously released LPL in heart perfusates to chromatography on heparin-agarose, which separates the active and inactive forms of the lipase. The amount of lipase protein released remained relatively constant on changes in the nutritional state and/or blockade of transcription, but the distribution between the active and inactive forms changed. Less of the LPL protein was in the active form in perfusates from hearts from fed compared with fasted rats. When glucose was given to fasted rats the proportion of LPL protein in the active form decreased. Actinomycin D increased the proportion that was active, in accord with the hypothesis that the message for a rapidly turning over LPL-controlling protein was being removed.
Wu
Gengshu
G
Department of Medical Biosciences, Physiological Chemistry, Umeå University, Umeå, Sweden.
Zhang
Liyan
L
Gupta
Jitendra
J
Olivecrona
Gunilla
G
Olivecrona
Thomas
T
D000273:Adipose Tissue / Q000201:enzymology / Q000378:metabolism*; D000818:Animals; D004789:Enzyme Activation / Q000235:genetics; D006321:Heart / Q000502:physiology; D006493:Heparin / Q000378:metabolism; D008055:Lipids / Q000097:blood; D008071:Lipoprotein Lipase / Q000378:metabolism*; D008297:Male; D009206:Myocardium / Q000201:enzymology*; D009928:Organ Specificity; D010477:Perfusion; D051381:Rats; D017207:Rats, Sprague-Dawley; D014158:Transcription, Genetic / Q000187:drug effects / Q000502:physiology*
D008055:Lipids; D006493:Heparin; D008071:Lipoprotein Lipase