Mammalian Genome

, Volume 20, Issue 2, pp 71–82

Genetic factors for resistance to diet-induced obesity and associated metabolic traits on mouse chromosome 17

  • Carrie A. Millward
  • Lindsay C. Burrage
  • Haifeng Shao
  • David S. Sinasac
  • Jean H. Kawasoe
  • Annie E. Hill-Baskin
  • Sheila R. Ernest
  • Aga Gornicka
  • Chang-Wen Hsieh
  • Sorana Pisano
  • Joseph H. Nadeau
  • Colleen M. Croniger
Article

DOI: 10.1007/s00335-008-9165-2

Cite this article as:
Millward, C.A., Burrage, L.C., Shao, H. et al. Mamm Genome (2009) 20: 71. doi:10.1007/s00335-008-9165-2

Abstract

Obesity is associated with increased susceptibility to dyslipidemia, insulin resistance, and hypertension, a combination of traits that comprise the traditional definition of the metabolic syndrome. Recent evidence suggests that obesity is also associated with the development of nonalcoholic fatty liver disease (NAFLD). Despite the high prevalence of obesity and its related conditions, their etiologies and pathophysiology remains unknown. Both genetic and environmental factors contribute to the development of obesity and NAFLD. Previous genetic analysis of high-fat, diet-induced obesity in C57BL/6J (B6) and A/J male mice using a panel of B6-ChrA/J/NaJ chromosome substitution strains (CSSs) demonstrated that 17 CSSs conferred resistance to high-fat, diet-induced obesity. One of these CSS strains, CSS-17, which is homosomic for A/J-derived chromosome 17, was analyzed further and found to be resistant to diet-induced steatosis. In the current study we generated seven congenic strains derived from CCS-17, fed them either a high-fat, simple-carbohydrate (HFSC) or low-fat, simple-carbohydrate (LFSC) diet for 16 weeks and then analyzed body weight and related traits. From this study we identified several quantitative trait loci (QTLs). On a HFSC diet, Obrq13 protects against diet-induced obesity, steatosis, and elevated fasting insulin and glucose levels. On the LFSC diet, Obrq13 confers lower hepatic triglycerides, suggesting that this QTL regulates liver triglycerides regardless of diet. Obrq15 protects against diet-induced obesity and steatosis on the HFSC diet, and Obrq14 confers increased final body weight and results in steatosis and insulin resistance on the HFSC diet. In addition, on the LFSC diet, Obrq 16 confers decreased hepatic triglycerides and Obrq17 confers lower plasma triglycerides on the LFSC diet. These congenic strains provide mouse models to identify genes and metabolic pathways that are involved in the development of NAFLD and aspects of diet-induced metabolic syndrome.

Supplementary material

335_2008_9165_MOESM1_ESM.tif (13.5 mb)
Supplementary Figure 1. Food intake on HFSC diet. Food intakes were measured weekly during the HFSC diet study. The values are the mean ± SEM for n = 8-22 mice per group and are represented as grams per mouse per day. (*< 0.005 compared to B6, Bonferonni’s correction for multiple testing). (abbreviations: B6 for C57BL/6J, A17 for CSS-17, C1 for 17C1, C2 for 17C2, C3 for 17C3, C4 for 17C4, C5 for 17C5, C6 for 17C6 and C7 for 17C7). (TIFF 13873 kb)
335_2008_9165_MOESM2_ESM.tif (12.2 mb)
Supplementary Table 1. Markers used for congenic panel of CSS-17. Seven congenic strains were generated. All primer sequences for micorsatellite markers were obtained from the Mouse Genome Informatics website http://www.informatics.jax.org/. (TIFF 12497 kb)
335_2008_9165_MOESM3_ESM.tif (26.9 mb)
Supplementary Table 2 Metabolic analysis of CSS-17 and congenic panel on high fat diet. Mice were fed a HFSC diet for 16 weeks and fasted overnight. The values are the mean±SEM for each strain tested (n = 8-22 mice per group). (a< 0.005 for 17C1 compared to B6, b< 0.005 for 17C5 compared to 17C6, c< 0.005 for 16C6 to 17C7 with Bonferonni’s correction for multiple testing) (Abbreviations are as follows TG, triglycerides; FFA, free fatty acids; CHOL, cholesterol). (TIFF 27508 kb)
335_2008_9165_MOESM4_ESM.tif (16.8 mb)
Supplementary Table 3. Metabolic analysis of CSS-17 and congenic panel on LFSC diet. Mice were fed a LFSC diet for 16 weeks and fasted overnight. The values are the mean±SEM for each strain tested (n = 8-15 mice per group). (a< 0.005 for 17C1 compared to B6, b< 0.005 for 17C2 compared to 17C1, c< 0.005 for 16C4 to 17C3 with Bonferonni’s correction for multiple testing) (TIFF 17245 kb)

Copyright information

© Springer Science+Business Media, LLC 2008

Authors and Affiliations

  • Carrie A. Millward
    • 1
  • Lindsay C. Burrage
    • 2
  • Haifeng Shao
    • 2
  • David S. Sinasac
    • 2
  • Jean H. Kawasoe
    • 2
  • Annie E. Hill-Baskin
    • 2
  • Sheila R. Ernest
    • 2
  • Aga Gornicka
    • 1
  • Chang-Wen Hsieh
    • 1
  • Sorana Pisano
    • 1
  • Joseph H. Nadeau
    • 2
  • Colleen M. Croniger
    • 1
  1. 1.Department of NutritionCase Western Reserve University School of MedicineClevelandUSA
  2. 2.Department of GeneticsCase Western Reserve University School of MedicineClevelandUSA

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