: Lipids, stored as triacylglycerol (TAG), play an essential role as a reserve of metabolic energy. In holometabolous insects, these reserves mainly accumulate during the larval stage in the form of TAG in the fat body. The digestion of fatty acid (FA) containing lipids and their processing in the midgut and transport to the fat body for storage are critical to insect development. Dietary cholesterol, or sterols that can be converted to cholesterol, are critical for insects because they cannot make sterols de riovo. Therefore, the absorption of sterols and their transport to tissues is also critical to insect development. Over the past several years we have made substantial progress in elucidating the general outline of the metabolic pathways involved in these processes. The critical unresolved issues include: 1) The mechanism by which FA and sterols are absorbed from the lumen into midgut enterocytes. 2) The mechanisms involved in lipid transfer between the hemolymph lipoprotein lipophorin and tissues. 3) The regulation of lipid export from midgut and lipid storage in the fat body. We propose to elucidate the mechanisms involved in lipid absorption from the midgut lumen and transport to sites of storage in the fat body using Manduca sexta larvae as a model insect through pursuit of the following specific aims: ? ? Specific aim 1. To clone and characterize fatty acid and sterol carrier proteins from the midgut. We will elucidate the role of FA and sterol transport proteins in lipid absorption from the midgut lumen into midgut epithelium.
Specific aim 2. To establish the mechanism of DAG transport. We will critically test the role of lipophorin receptors and LTP in the transfer of DAG between tissues and lipophorin and we will develop and test quantitatively a model for DAG transport.
Specific aim 3. To establish the mechanism of cholesterol transport. We will critically test the mass action hypothesis for the regulation of cholesterol homeostasis in larval M. sexta.
Specific aim 4. To clone and characterize lipophorin receptors from the midgut and the fat body. We will elucidate the role of lipophorin receptors in lipid transport.

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Research Project (R01)
Project #
5R01GM050008-12
Application #
6912693
Study Section
Special Emphasis Panel (ZRG1-TMP (01))
Program Officer
Chin, Jean
Project Start
1993-07-01
Project End
2006-06-30
Budget Start
2005-07-01
Budget End
2006-06-30
Support Year
12
Fiscal Year
2005
Total Cost
$361,081
Indirect Cost
Name
University of Arizona
Department
Biochemistry
Type
Schools of Arts and Sciences
DUNS #
806345617
City
Tucson
State
AZ
Country
United States
Zip Code
85721
Gondim, Katia C; Pennington, James E; Meyer-Fernandes, José Roberto et al. (2013) Effect of starvation on lipophorin density in fifth instar larval Manduca sexta. Arch Insect Biochem Physiol 84:145-56
Ziegler, R; Isoe, J; Moore, W et al. (2011) The putative AKH receptor of the tobacco hornworm, Manduca sexta, and its expression. J Insect Sci 11:40
Canavoso, Lilian E; Yun, Hwa Kyung; Jouni, Zeina E et al. (2004) Lipid transfer particle mediates the delivery of diacylglycerol from lipophorin to fat body in larval Manduca sexta. J Lipid Res 45:456-65
Jouni, Z E; Takada, N; Gazard, J et al. (2003) Transfer of cholesterol and diacylglycerol from lipophorin to Bombyx mori ovarioles in vitro: role of the lipid transfer particle. Insect Biochem Mol Biol 33:145-53
Pennington, James E; Wells, Michael A (2002) Triacylglycerol-rich lipophorins are found in the dipteran infraorder Culicomorpha, not just in mosquitoes. J Insect Sci 2:15
Yun, Hwa Kyung; Jouni, Zeina E; Wells, Michael A (2002) Characterization of cholesterol transport from midgut to fat body in Manduca sexta larvae. Insect Biochem Mol Biol 32:1151-8
Jouni, Zeina E; McGill, Brandon; Wells, Michael A (2002) Beta-cyclodextrin facilitates cholesterol efflux from larval Manduca sexta fat body and midgut in vitro. Comp Biochem Physiol B Biochem Mol Biol 132:699-709
Jouni, Zeina E; Zamora, Jorge; Wells, Michael A (2002) Absorption and tissue distribution of cholesterol in Manduca sexta. Arch Insect Biochem Physiol 49:167-75
Canavoso, L E; Wells, M A (2001) Role of lipid transfer particle in delivery of diacylglycerol from midgut to lipophorin in larval Manduca sexta. Insect Biochem Mol Biol 31:783-90
Canavoso, L E; Jouni, Z E; Karnas, K J et al. (2001) Fat metabolism in insects. Annu Rev Nutr 21:23-46

Showing the most recent 10 out of 26 publications