Abstract

The long term goals of the project are to define the physiology and biochemistry of fat digestion.
The specific aims of the proposal are: (1) define the role of pancreatic lipase related protein 2 (PLRP2), a homologue of pancreatic triglyceride lipase, in fat digestion at various ages by characterizing fat utilization in PLRP2 deficient mice. The approach to this aim will be to determine fecal fat excretion in PLRP2 deficient mice at various stages of development and after being fed different levels of fat. (2) delineate the role of colipase in dietary fat digestion by ablating the gene encoding procolipase in mice. These mice will be created and the absence of colipase expression determined by mRNA and protein analysis. Fat absorption will be ascertained in the deficient mice; (3) demonstrate that enterostatin, the activation peptide of procolipase, mediates satiety and controls obesity by creating enterostatin deficient mice with gene ablation and transgenic techniques; and (4) characterize the receptor for enterostatin on neuronal and nonneuronal cells by measuring binding of radiolabeled enterostatin. Detailed knowledge of the receptor properties may reveal a novel approach to obesity treatment and fat satiety.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Type
Research Project (R01)
Project #
5R01DK053100-03
Application #
6177966
Study Section
Nutrition Study Section (NTN)
Program Officer
May, Michael K
Project Start
1998-06-01
Project End
2002-05-31
Budget Start
2000-06-01
Budget End
2002-05-31
Support Year
3
Fiscal Year
2000
Total Cost
$204,137
Indirect Cost

  Institution

Name
Washington University
Department
Pediatrics
Type
Schools of Medicine
DUNS #
062761671
City
Saint Louis
State
MO
Country
United States
Zip Code
63130

  Publications

Alves, Bryce N; Marshall, Kristen; Tamang, David L et al. (2009) Lipid-dependent cytotoxicity by the lipase PLRP2 and by PLRP2-positive cytotoxic T lymphocytes (CTLs). Cell Biochem Funct 27:296-308
Alves, Bryce N; Leong, Jeff; Tamang, David L et al. (2009) Pancreatic lipase-related protein 2 (PLRP2) induction by IL-4 in cytotoxic T lymphocytes (CTLs) and reevaluation of the negative effects of its gene ablation on cytotoxicity. J Leukoc Biol 86:701-12
Gonzalez, Nieves; Moody, Terry W; Igarashi, Hisato et al. (2008) Bombesin-related peptides and their receptors: recent advances in their role in physiology and disease states. Curr Opin Endocrinol Diabetes Obes 15:58-64
Miller, Rita; Lowe, Mark E (2008) Carboxyl ester lipase from either mother's milk or the pancreas is required for efficient dietary triglyceride digestion in suckling mice. J Nutr 138:927-30
Schumann, Michael; Nakagawa, Tomoo; Mantey, Samuel A et al. (2008) Function of non-visual arrestins in signaling and endocytosis of the gastrin-releasing peptide receptor (GRP receptor). Biochem Pharmacol 75:1170-85
Jensen, R T; Battey, J F; Spindel, E R et al. (2008) International Union of Pharmacology. LXVIII. Mammalian bombesin receptors: nomenclature, distribution, pharmacology, signaling, and functions in normal and disease states. Pharmacol Rev 60:1-42
Gonzalez, Nieves; Hocart, Simon J; Portal-Nunez, Sergio et al. (2008) Molecular basis for agonist selectivity and activation of the orphan bombesin receptor subtype 3 receptor. J Pharmacol Exp Ther 324:463-74
Berna, Marc J; Jensen, Robert T (2007) Role of CCK/gastrin receptors in gastrointestinal/metabolic diseases and results of human studies using gastrin/CCK receptor agonists/antagonists in these diseases. Curr Top Med Chem 7:1211-31
Berna, Marc J; Tapia, Jose A; Sancho, Veronica et al. (2007) Progress in developing cholecystokinin (CCK)/gastrin receptor ligands that have therapeutic potential. Curr Opin Pharmacol 7:583-92
Borowitz, Drucy; Durie, Peter R; Clarke, Lane L et al. (2005) Gastrointestinal outcomes and confounders in cystic fibrosis. J Pediatr Gastroenterol Nutr 41:273-85

Showing the most recent 10 out of 16 publications