Skip to main content
SpringerLink
Log in

Increased physical activity cosegregates with higher intake of carbohydrate and total calories in a subcongenic mouse strain

  • Published:
Mammalian Genome Aims and scope Submit manuscript

Abstract

C57BL/6 J (B6) and CAST/EiJ (CAST), the inbred strain derived from M. musculus castaneus, differ in nutrient intake behaviors, including dietary fat and carbohydrate consumption in a two-diet-choice paradigm. Significant quantitative trait loci (QTLs) for carbohydrate (Mnic1) and total energy intake (Kcal2) are present between these strains on chromosome (Chr) 17. Here we report the refinement of the Chr 17 QTL in a subcongenic strain of the B6.CAST-D17Mit19-D17Mit91 congenic mice described previously. This new subcongenic strain possesses CAST Chr 17 donor alleles from 4.8 to 45.4 Mb on a B6 background. Similar to CAST, the subcongenic mice exhibit increased carbohydrate and total calorie intake per body weight, while fat intake remains equivalent. Unexpectedly, this CAST genomic segment also confers two new physical activity phenotypes: 22% higher spontaneous physical activity levels and significantly increased voluntary wheel-running activity compared with the parental B6 strain. Overall, these data suggest that gene(s) involved in carbohydrate preference and increased physical activity are contained within the proximal region of Chr 17. Interval-specific microarray analysis in hypothalamus and skeletal muscle revealed differentially expressed genes within the subcongenic region, including neuropeptide W (Npw); glyoxalase I (Glo1); cytochrome P450, family 4, subfamily f, polypeptide 1 (Cyp4f15); phospholipase A2, group VII (Pla2g7); and phosphodiesterase 9a (Pde9a). This subcongenic strain offers a unique model for dissecting the contributions and possible interactions among genes controlling food intake and physical activity, key components of energy balance.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4

Similar content being viewed by others

References

  • Albarado DC, McClaine J, Stephens JM, Mynatt RL, Ye J et al (2004) Impaired coordination of nutrient intake and substrate oxidation in melanocortin-4 receptor knockout mice. Endocrinology 145:243–252

    Article  CAS  PubMed  Google Scholar 

  • Berthoud HR, Lenard NR (2008) Central and peripheral regulation of food intake and physical activity: pathways and genes. Obesity 16(Suppl 3):S11–S22

    PubMed  Google Scholar 

  • Bolstad BM, Irizarry RA, Astrand M, Speed TP (2003) A comparison of normalization methods for high density oligonucleotide array data based on variance and bias. Bioinformatics 19:185–193

    Article  CAS  PubMed  Google Scholar 

  • Cai G, Cole SA, Bastarrachea RA, Maccluer JW, Blangero J et al (2004) Quantitative trait locus determining dietary macronutrient intakes is located on human chromosome 2p22. Am J Clin Nutr 80:1410–1414

    CAS  PubMed  Google Scholar 

  • Cai G, Cole SA, Butte N, Bacino C, Diego V et al (2006) A quantitative trait locus on chromosome 18q for physical activity and dietary intake in Hispanic children. Obesity (Silver Spring) 14:1596–1604

    Article  CAS  Google Scholar 

  • Chiu S, Kim K, Haus KA, Espinal GM, Millon LV et al (2007) Identification of positional candidate genes for body weight and adiposity in subcongenic mice. Physiol Genomics 31:7585

    Google Scholar 

  • Choquette AC, Lemieux S, Tremblay A, Chagnon YC, Bouchard C et al (2008) Evidence of a quantitative trait locus for energy and macronutrient intakes on chromosome 3q27.3: the Quebec Family Study. Am J Clin Nutr 88:1142–1148

    CAS  PubMed  Google Scholar 

  • Collaku A, Rankinen T, Rice T, Leon AS, Rao DC et al (2004) A genome-wide linkage scan for dietary energy and nutrient intakes: the Health, Risk Factors, Exercise Training, and Genetics (HERITAGE) Family Study. Am J Clin Nutr 79:881–886

    CAS  PubMed  Google Scholar 

  • Cui X, Kawashima H, Barclay TB, Peters JM, Gonzalez FJ et al (2001) Molecular cloning and regulation of expression of two novel mouse CYP4F genes: expression in peroxisome proliferator-activated receptor α-deficient mice upon lipopolysaccharide and clofibrate challenges. J Pharmacol Exp Ther 296:542–550

    CAS  PubMed  Google Scholar 

  • Delahunty KM, Shultz KL, Gronowicz GA, Koczon-Jaremko B, Adamo ML et al (2006) Congenic mice provide in vivo evidence for a genetic locus that modulates serum insulin-like growth factor-I and bone acquisition. Endocrinology 147:3915–3923

    Article  CAS  PubMed  Google Scholar 

  • Faith MS, Rha SS, Neale MC, Allison DB (1999) Evidence for genetic influences on human energy intake: results from a twin study using measured observations. Behav Genet 29:145–154

    Article  CAS  PubMed  Google Scholar 

  • Farber CR, Medrano JF (2007) Fine mapping reveals sex bias in quantitative trait loci affecting growth, skeletal muscle size and obesity-related traits on mouse chromosomes 2 and 11. Genetics 175:349–360

    Article  PubMed  Google Scholar 

  • Furuse T, Takano-Shimizu T, Moriwaki K, Shiroishi T, Koide T (2002) QTL analyses of spontaneous activity by using mouse strains from Mishima battery. Mamm Genome 13:411–415

    Article  CAS  PubMed  Google Scholar 

  • Harri M, Lindblom J, Malinen H, Hyttinen M, Lapvetelainen T et al (1999) Effect of access to a running wheel on behavior of C57BL/6 J mice. Lab Anim Sci 49:401–405

    CAS  PubMed  Google Scholar 

  • Hofstetter JR, Possidente B, Mayeda AR (1999) Provisional QTL for circadian period of wheel running in laboratory mice: quantitative genetics of period in RI mice. Chronobiol Int 16:269–279

    Article  CAS  PubMed  Google Scholar 

  • Ishimori N, Li R, Kelmenson PM, Korstanje R, Walsh KA et al (2004) Quantitative trait loci that determine plasma lipids and obesity in C57BL/6 J and 129S1/SvImJ inbred mice. J Lipid Res 45:1624–1632

    Article  CAS  PubMed  Google Scholar 

  • Jerez-Timaure NC, Eisen EJ, Pomp D (2005) Fine mapping of a QTL region with large effects on growth and fatness on mouse chromosome 2. Physiol Genomics 21:411–422

    Article  CAS  PubMed  Google Scholar 

  • Kumar KG, Smith Richards BK (2008) Transcriptional profiling of Chromosome 17 QTL for carbohydrate and total calorie intake in a mouse congenic strain reveals candidate genes and pathways. J Nutrigenet Nutrigenomics 1:155–171

    Article  CAS  Google Scholar 

  • Kumar KG, Poole AC, York B, Volaufova J, Zuberi A et al (2007a) Quantitative trait loci for carbohydrate and total energy intake on mouse chromosome 17: congenic strain confirmation and candidate gene analyses (Glo1, Glp1r). Am J Physiol Regul Integr Comp Physiol 292:R207–R216

    CAS  PubMed  Google Scholar 

  • Kumar KG, Zuberi A, Smith Richards BK (2007b) A unique genetic locus on mouse Chromosome 17 influences energy intake, carbohydrate preference, and spontaneous physical activity in a subcongenic strain. Obes Res 15:A183

    Google Scholar 

  • Kumar KG, Byerley L, Volaufova J, Drucker DJ, Churchill GA et al (2008) Genetic variation in Glp1r expression influences the rate of gastric emptying in mice. Am J Physiol Regul Integr Comp Physiol 294:R262–R371

    Google Scholar 

  • Leiter EH, Reifsnyder PC, Zhang W, Pan HJ, Xiao Q et al (2006) Differential endocrine responses to rosiglitazone therapy in new mouse models of type 2 diabetes. Endocrinology 147:919–926

    Article  CAS  PubMed  Google Scholar 

  • Levine AS, Winsky-Sommerer R, Huitron-Resendiz S, Grace MK, de Lecea L (2005) Injection of neuropeptide W into paraventricular nucleus of hypothalamus increases food intake. Am J Physiol Regul Integr Comp Physiol 288:R1727–R1732

    CAS  PubMed  Google Scholar 

  • Pavlidis P (2003) Using ANOVA for gene selection from microarray studies of the nervous system. Methods 31:282–289

    Article  CAS  PubMed  Google Scholar 

  • Raber P, Del Canho S, Darvasi A, Devor M (2006) Mice congenic for a locus that determines phenotype in the neuroma model of neuropathic pain. Exp Neurol 202:200–206

    Article  CAS  PubMed  Google Scholar 

  • Rankinen T, Bouchard C (2006) Genetics of food intake and eating behavior phenotypes in humans. Annu Rev Nutr 26:413–434

    Article  CAS  PubMed  Google Scholar 

  • Reed DR, Bachmanov AA, Beauchamp GK, Tordoff MG, Price RA (1997) Heritable variation in food preferences and their contribution to obesity. Behav Genet 27:373–387

    Article  CAS  PubMed  Google Scholar 

  • Riachi M, Himms-Hagen J, Harper ME (2004) Percent relative cumulative frequency analysis in indirect calorimetry: application to studies of transgenic mice. Can J Physiol Pharmacol 82:1075–1083

    Article  CAS  PubMed  Google Scholar 

  • Sakkou M, Wiedmer P, Anlag K, Hamm A, Seuntjens E et al (2007) A role for brain-specific homeobox factor Bsx in the control of hyperphagia and locomotor behavior. Cell Metab 5:450–463

    Article  CAS  PubMed  Google Scholar 

  • Sherwin CM (1998) Voluntary wheel running: a review and novel interpretation. Anim Behav 56:11–27

    Article  PubMed  Google Scholar 

  • Shimomura Y, Harada M, Goto M, Sugo T, Matsumoto Y et al (2002) Identification of neuropeptide W as the endogenous ligand for orphan G-protein-coupled receptors GPR7 and GPR8. J Biol Chem 277:35826–35832

    Article  CAS  PubMed  Google Scholar 

  • Singh G, Davenport AP (2006) Neuropeptide B and W: neurotransmitters in an emerging G-protein-coupled receptor system. Br J Pharmacol 148:1011–1041

    Article  Google Scholar 

  • Smith BK, Andrews PK, West DB (2000) Macronutrient self-selection in thirteen mouse strains. Am J Physiol 278:R797–R805

    CAS  Google Scholar 

  • Smith Richards BK, Belton BN, Poole AC, Mancuso JJ, Churchill GA et al (2002) QTL analysis of self-selected macronutrient diet intake: fat, carbohydrate, and total kilocalories. Physiol Genomics 11:205–217

    CAS  PubMed  Google Scholar 

  • Stylianou IM, Korstanje R, Li R, Sheehan S, Paigen B et al (2006) Quantitative trait locus analysis for obesity reveals multiple networks of interacting loci. Mamm Genome 17:22–36

    Article  PubMed  Google Scholar 

  • Tafti M, Petit B, Chollet D, Neidhart E, de Bilbao F et al (2003) Deficiency in short-chain fatty acid beta-oxidation affects theta oscillations during sleep. Nat Genet 34:320–325

    Article  CAS  PubMed  Google Scholar 

  • Tanaka H, Yoshida T, Miyamoto N, Motoike T, Kurosu H et al (2003) Characterization of a family of endogenous neuropeptide ligands for the G protein-coupled receptors GPR7 and GPR8. Proc Natl Acad Sci U S A 100:6251–6256

    Article  CAS  PubMed  Google Scholar 

  • Thornalley PJ (2006) Unease on the role of glyoxalase 1 in high-anxiety-related behaviour. Trends Mol Med 12:195–199

    Article  CAS  PubMed  Google Scholar 

  • Thornalley PJ (2008) Protein and nucleotide damage by glyoxal and methylglyoxal in physiological systems—role in ageing and disease. Drug Metabol Drug Interact 23:125–150

    CAS  PubMed  Google Scholar 

  • Warden CH, Stone S, Chiu S, Diament AL, Corva P et al (2004) Identification of a congenic mouse line with obesity and body length phenotypes. Mamm Genome 15:460–471

    Article  CAS  PubMed  Google Scholar 

  • Wareham NJ, Young EH, Loos RJ (2008) Epidemiological study designs to investigate gene-behavior interactions in the context of human obesity. Obesity (Silver Spring) 16(Suppl 3):S66–S71

    Article  Google Scholar 

Download references

Acknowledgments

This work was supported by grant DK53113 (to BKSR) from the National Institutes of Health and was partially supported by CNRU Center grant 1P30 DK072476 sponsored by NIDDK. We thank Candice Pereira and Stephannie Ruiz for technical assistance in these studies. A preliminary report was published in abstract form (Kumar et al. 2007b).

Author information

Authors and Affiliations

  1. Pennington Biomedical Research Center, Louisiana State University System, 6400 Perkins Road, Baton Rouge, LA, 70808-4124, USA

    K. Ganesh Kumar, Lisa M. DiCarlo, Aamir R. Zuberi & Brenda K. Smith Richards

  2. Biostatistics Program, Louisiana State University Health Sciences Center, New Orleans, LA, 70112, USA

    Julia Volaufova

Authors
  1. K. Ganesh Kumar
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Lisa M. DiCarlo
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Julia Volaufova
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Aamir R. Zuberi
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Brenda K. Smith Richards
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Brenda K. Smith Richards.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Kumar, K.G., DiCarlo, L.M., Volaufova, J. et al. Increased physical activity cosegregates with higher intake of carbohydrate and total calories in a subcongenic mouse strain. Mamm Genome 21, 52–63 (2010). https://doi.org/10.1007/s00335-009-9243-0

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00335-009-9243-0

Keywords

Search

Navigation