Abstract

Obesity is a serious independent risk factor for a number of disorders including diabetes, hypertension and cardiovascular disease. Development of effective measures to treat or prevent obesity will have a significant impact upon the incidence of these other diseases. Obesity is caused by a number of factors. There is a significant genetic component affecting the risk for the development of obesity and environmental factors such as dietary fat content also influence its expression. Interactions of predisposing genes with dietary fat may also be very important in determining the risk for obesity in an individual. The long-term goal of this project is to identify and characterize the genes which predispose for the development of obesity. We propose to use a mouse model initially to identify these genes and then to determine if the same genes or metabolic pathways are controlling the expression of human obesity. The overall approach which we propose to take is the mapping of quantitative trait loci (QTLs) in mouse populations segregating for sensitivity to dietary obesity. In this application, the specific aims are to: A. complete a linkage map of the loci controlling differential sensitivity to dietary obesity in the AKR/J x SWR/J mouse model. B. evaluate the role of specific genetic loci linked to dietary obesity in the AKR/J x SWR/J model in several other genetic models of dietary obesity. C. develop congenic strains for each locus, and several combinations of loci, in order to determine their relative quantitative contribution to the phenotype of dietary obesity. D. evaluate the role of specific candidate genes at these loci.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Type
Research Project (R01)
Project #
1R01DK045895-01A1
Application #
2145127
Study Section
Nutrition Study Section (NTN)
Project Start
1994-09-15
Project End
1997-08-31
Budget Start
1994-09-15
Budget End
1995-08-31
Support Year
1
Fiscal Year
1994
Total Cost
Indirect Cost

  Institution

Name
Lsu Pennington Biomedical Research Center
Department
Type
Organized Research Units
DUNS #
City
Baton Rouge
State
LA
Country
United States
Zip Code
70808

  Publications

Dhar, Madhu; Hauser, Loren; Johnson, Dabney (2002) An aminophospholipid translocase associated with body fat and type 2 diabetes phenotypes. Obes Res 10:695-702
Smith, B K; Volaufova, J; West, D B (2001) Increased flavor preference and lick activity for sucrose and corn oil in SWR/J vs. AKR/J mice. Am J Physiol Regul Integr Comp Physiol 281:R596-606
Dhar, M; Webb, L S; Smith, L et al. (2000) A novel ATPase on mouse chromosome 7 is a candidate gene for increased body fat. Physiol Genomics 4:93-100
West, D B; Iakougova, O; Olsson, C et al. (2000) Mouse genetics/genomics: an effective approach for drug target discovery and validation. Med Res Rev 20:216-30
Smith, B K; Andrews, P K; West, D B (2000) Macronutrient diet selection in thirteen mouse strains. Am J Physiol Regul Integr Comp Physiol 278:R797-805
Smith, B K; Andrews, P K; York, D A et al. (1999) Divergence in proportional fat intake in AKR/J and SWR/J mice endures across diet paradigms. Am J Physiol 277:R776-85
York, B; Truett, A A; Monteiro, M P et al. (1999) Gene-environment interaction: a significant diet-dependent obesity locus demonstrated in a congenic segment on mouse chromosome 7. Mamm Genome 10:457-62
West, D B; York, B (1998) Dietary fat, genetic predisposition, and obesity: lessons from animal models. Am J Clin Nutr 67:505S-512S
Smith, B K; West, D B; York, D A (1997) Carbohydrate versus fat intake: differing patterns of macronutrient selection in two inbred mouse strains. Am J Physiol 272:R357-62
York, B; Lei, K; West, D B (1997) Inherited non-autosomal effects on body fat in F2 mice derived from an AKR/J x SWR/J cross. Mamm Genome 8:726-30

Showing the most recent 10 out of 13 publications