Lipids, stored as triacylglycerol (TG), play an essential role as reserve of metabolic energy in insects. Utilization of fat body TG stores requires TG hydrolysis (lipolysis). Because fatty acids provide energy to other tissues as well as to the fat body cell, lipolysis must be coupled to multiple metabolic pathways. The long-term goal of this project is to understand the mechanism of regulation of lipolysis. During the previous period we identified two key components of the lipolytic pathway in insects. The main lipase found in the insect fat body, TG-lipase (TGL) homolog to Drosophila melanogaster CG8552, and a lipid droplet-associated protein, Lsd1, whose phosphorylation stimulates the rate of lipolysis. Lsd1 is one of the two PAT proteins, Lsd1 and Lsd2, of insect lipid droplets and plays a major role in the regulation of lipolysis. Lsd1 contains multiple conserved phosphorylation sites that regulate its activity. Lsd1 also has structurally conserved domains that are expected to play a role in its interaction with lipases and regulatory proteins and thus in the regulation of lipolysis. One of the goals of this project is to dissect the role of different regions of the Lsd1 molecule in the regulation of lipolysis. Other cytosolic and lipid droplet proteins, such as Lsd2, are expected to be involved in the regulation of lipolysis. This project also proposes to identify some of these proteins using a proteomic approach coupled to specific interaction assays and global studies to define differences in the protein composition of lipid droplets from several insects. Strong evidence indicating that the rate of lipolysis in the insect fat body is affected by the redox state of adipocytes led us to propose the investigation of this mechanism. Because the rate of TG hydrolysis must be modulated by signals originated from different pathways, we hypothesize that the redox state of the fat body cell, which is sensitive to multiple metabolic changes, plays a major role in the regulation of TG hydrolysis. In this project we will study the mechanism by which the redox state of the cell affects lipolysis. These studies will contribute to the understanding of the regulation of the utilization of energy stores in insects. This aspect of the biology of insects may be important to find mechanisms of control of insects that act as vectors of human diseases.

Public Health Relevance

Energy metabolism and its regulation are key processes defining insect survival and reproduction. TGs are the predominant form of energy storage in all animals. The ability to store and release this energy involves a carefully regulated balance between TG synthesis and hydrolysis. Specialized mechanisms are expected in insects, including vectors of human diseases, to meet their unique metabolic needs, such as the capacity to mobilize massive amounts of lipid in a short period of time. These metabolic distinctions must be reflected in the molecular mechanisms involved in TG mobilization in insects. The long term goal of this project is to achieve a clear understanding of the regulation of triacylglycerol metabolism in insects.

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Research Project (R01)
Project #
5R01GM064677-09
Application #
8204455
Study Section
Special Emphasis Panel (ZRG1-IDM-M (02))
Program Officer
Chin, Jean
Project Start
2002-02-01
Project End
2013-11-30
Budget Start
2011-12-01
Budget End
2013-11-30
Support Year
9
Fiscal Year
2012
Total Cost
$220,036
Indirect Cost
$71,061
Name
Oklahoma State University Stillwater
Department
Biochemistry
Type
Schools of Earth Sciences/Natur
DUNS #
049987720
City
Stillwater
State
OK
Country
United States
Zip Code
74078
Soulages, Jose L; Wu, Zengying; Firdaus, Sarah J et al. (2015) Monoacylglycerol and diacylglycerol acyltransferases and the synthesis of neutral glycerides in Manduca sexta. Insect Biochem Mol Biol 62:194-210
Lin, Penghui; Chen, Xiao; Moktan, Hem et al. (2014) Membrane attachment and structure models of lipid storage droplet protein 1. Biochim Biophys Acta 1838:874-81
Arrese, Estela L; Saudale, Fredy Z; Soulages, Jose L (2014) Lipid Droplets as Signaling Platforms Linking Metabolic and Cellular Functions. Lipid Insights 7:7-16
Wu, Zengying; Soulages, Jose L; Joshi, Bharat D et al. (2014) TGL-mediated lipolysis in Manduca sexta fat body: possible roles for lipoamide-dehydrogenase (LipDH) and high-density lipophorin (HDLp). Insect Biochem Mol Biol 45:58-68
Soulages, Jose L; Firdaus, Sarah J; Hartson, Steve et al. (2012) Developmental changes in the protein composition of Manduca sexta lipid droplets. Insect Biochem Mol Biol 42:305-20
Arrese, Estela L; Soulages, Jose L (2010) Insect fat body: energy, metabolism, and regulation. Annu Rev Entomol 55:207-25
Arrese, Estela L; Howard, Alisha D; Patel, Rajesh T et al. (2010) Mobilization of lipid stores in Manduca sexta: cDNA cloning and developmental expression of fat body triglyceride lipase, TGL. Insect Biochem Mol Biol 40:91-9
Arrese, Estela L; Rivera, Laticia; Hamada, Masakazu et al. (2008) Purification and characterization of recombinant lipid storage protein-2 from Drosophila melanogaster. Protein Pept Lett 15:1027-32
Arrese, Estela L; Rivera, Laticia; Hamada, Masakazu et al. (2008) Function and structure of lipid storage droplet protein 1 studied in lipoprotein complexes. Arch Biochem Biophys 473:42-7
Arrese, Estela L; Mirza, Saima; Rivera, Laticia et al. (2008) Expression of lipid storage droplet protein-1 may define the role of AKH as a lipid mobilizing hormone in Manduca sexta. Insect Biochem Mol Biol 38:993-1000

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