Alternative lipid mobilization: the insect shuttle system.
Lipid mobilization in long-distance flying insects has revealed a novel concept for lipid transport in the circulatory system during exercise. Similar to energy generation for sustained locomotion in mammals, the work accomplished by non-stop flight activity is powered by oxidation of free fatty acids (FFA) derived from endogenous reserves of triacylglycerol. The transport form of the lipid, however, is diacylglycerol (DAG), which is delivered to the flight muscles associated with lipoproteins. In the insect system, the multifunctional lipoprotein, high-density lipophorin (HDLp) is loaded with DAG while additionally, multiple copies of the exchangeable apolipoprotein, apoLp-III, associate with the expanding particle. As a result, lipid-enriched low-density lipophorin (LDLp) is formed. At the flight muscles, LDLp-carried DAG is hydrolyzed and FFA are imported into the muscle cells for energy generation. The depletion of DAG from LDLp results in the recovery of both HDLp and apoLp-III, HDLp, identified which are reutilized for another cycle of DAG transport. A receptor for as a novel member of the vertebrate low-density lipoprotein (LDL) receptor family, does not seem to be involved in the lipophorin shuttle mechanism operative during flight activity. In addition, endocytosis of HDLp mediated by the insect receptor does not seem to follow the classical mammalian LDL pathway. Many structural elements of the lipid mobilization system in insects are similar to those in mammals. Domain structures of apoLp-I and apoLp-II, the non-exchangeable apolipoprotein components of HDLp, are related to apoB 100. ApoLp-III is a bundle of five amphipathic alpha-helices that binds to a lipid surface very similar to the four-helix bundle of the N-terminal domain of human apoE. Despite these similarities, the functioning of the insect lipoprotein in energy transport during flight activity is intriguingly different, since the TAG-rich mammalian lipoproteins play no role as a carrier of mobilized lipids during exercise and besides, these lipoproteins are not functioning as a reusable shuttle for lipid transport. On the other hand, the deviant behavior of similar molecules in a different biological system may provide a useful alternative model for studying the molecular basis of processes related to human disorders and disease.
van der Horst
Dick J
DJ
Department of Biochemical Physiology and Institute of Biomembranes, Utrecht University, Utrecht, The Netherlands. d.j.vanderhorst@bio.uu.nl
van Hoof
Dennis
D
van Marrewijk
Wil J A
WJ
Rodenburg
Kees W
KW
D000818:Animals; D001053:Apolipoproteins / Q000737:chemistry / Q000378:metabolism; D002352:Carrier Proteins / Q000737:chemistry / Q000378:metabolism*; D002460:Cell Line; D004705:Endocytosis / Q000502:physiology*; D000071438:Fatty Acid-Binding Protein 7; D050556:Fatty Acid-Binding Proteins; D005426:Flight, Animal / Q000502:physiology; D006801:Humans; D007313:Insecta / Q000502:physiology*; D050356:Lipid Metabolism; D008074:Lipoproteins / Q000737:chemistry / Q000378:metabolism; D009363:Neoplasm Proteins; D011487:Protein Conformation; D011973:Receptors, LDL / Q000737:chemistry / Q000378:metabolism; D025521:Tumor Suppressor Proteins
D001053:Apolipoproteins; D002352:Carrier Proteins; C107608:FABP7 protein, human; D000071438:Fatty Acid-Binding Protein 7; D050556:Fatty Acid-Binding Proteins; D008074:Lipoproteins; D009363:Neoplasm Proteins; D011973:Receptors, LDL; D025521:Tumor Suppressor Proteins; C042470:apolipophorin III