Quantitative Trait Loci for Regional Adiposity in Mouse Lines Divergently Selected for Food Intake

Rance, K. A.; Hambly, Catherine; Dalgleish, Gillian; Fustin, Jean‐Michel; Bünger, L.; Speakman, John R.

doi:10.1038/oby.2007.357

Cited by 6 publications

(4 citation statements)

References 69 publications

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“…A thrifty gene on Chromosome 14 defined by caloric efficiency was a dominant-acting genetic component of high-fat diet-induced obesity in a F2 intercross of C57BL/6 and 129S6/SvEv mice (Almind and Kahn, 2004). Finally, using a F2 intercross, QTL analyses of fat depots in mouse lines divergently selected for food intake revealed that Chromosomes 4 and 19 were associated with both white and brown adipose tissue depots, whereas Chromosome 9 was associated with only white adipose tissue depots (Rance et al, 2007). It would be of future interest to link underlying pharmacological control of fat intake with QTL analyses of highly-sensitive (e.g., SWR, DBA/2 ) and less-sensitive ( BALB/c ) strains.…”

Section: Discussionmentioning

confidence: 99%

Genetic variance contributes to dopamine and opioid receptor antagonist-induced inhibition of intralipid (fat) intake in inbred and outbred mouse strains

et al. 2010

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Preference for and intake of solid and emulsified fat (Intralipid) solutions vary across different mouse strains. Fat intake in rodents is inhibited by dopamine and opioid receptor antagonists, but any variation in these responses as a function of genetic background is unknown. Therefore, the present study compared the ability of dopamine D1-like (SCH23390) and general opioid (naltrexone) receptor antagonism to alter intake of fat emulsions (Intralipid) in mice. Two-h intakes of 5% Intralipid were measured (5-120 min) in seven inbred (BALB/c, C57BL/6, C57BL/10, DBA/2, SJL, SWR, 129P3) and one outbred (CD-1) mouse strains following treatment with vehicle, SCH23390 (50-1600 nmol/kg, ip) and naltrexone (0.001-5 mg/kg, sc). SCH23390 significantly, dosedependently and differentially reduced Intralipid intake at all five (DBA/2, SWR, CD-1), four (SJL, C57BL/6), three (129P3) and one (C57BL/10) of the doses tested, but failed to affect Intralipid intake in BALB/c mice. Naltrexone significantly, dose-dependently and differentially reduced Intralipid intake at all four (DBA/2), three (SWR, SJL), two (CD-1, C57BL/10) and one (C57BL/6, 129P3) of the doses tested, and also failed to affect Intralipid intake in BALB/cJ mice. SCH23390 and naltrexone were respectively 13.3-fold and 9.3-fold more potent in inhibiting Intralipid intake in the most sensitive (DBA/2) relative to the least sensitive (BALB/c) mouse strains. A strong positive relationship (r=0.91) was observed for the abilities of SCH23390 and naltrexone to inhibit Intralipid intake across strains. These findings indicate that dopaminergic and opioid signaling mechanisms differentially control Intralipid intake across different mouse strains, suggesting important genetic and pharmacological interactions in the short-term control of rewarding and post-ingestive consequences of fat intake.

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Section: Discussionmentioning

confidence: 99%

Genetic variance contributes to dopamine and opioid receptor antagonist-induced inhibition of intralipid (fat) intake in inbred and outbred mouse strains

et al. 2010

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“…It is recognized that sex Â genotype as well as sex Â genotype Â environment interactions play a critical evolutionary role in producing and maintaining genetic variation (Mackay 2001). Several sex Â QTL interactions have been reported, including those that influence tissue mass (Rance et al 2007), bone mineral density (Ishimori et al 2008), and pain responses (Mogil et al 1997). Given its magnitude and proximity to the MM locus, the triceps surae mass MMU11 QTL interaction with sex could prove beneficial for delineating the genetic architecture of MM.…”

Section: Discussionmentioning

confidence: 99%

QTL Underlying Voluntary Exercise in Mice: Interactions with the "Mini Muscle" Locus and Sex

Nehrenberg

Wang

Hannon

et al. 2009

Journal of Heredity

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Exercise improves many aspects of human health, yet many people remain inactive even when exercise is prescribed. We previously created a backcross (BC) between mice selectively bred for high levels of voluntary wheel running (VWR) and fixed for "mini muscle" (MM), a recessive mutation causing approximately 50% reduction in triceps surae mass. We previously showed that BC mice having the MM trait ran faster and further than mice without MM and that MM maps to chromosome 11. Here, we genotyped the BC with genome-wide single nucleotide polymorphisms to identify quantitative trait loci (QTL) controlling voluntary exercise and tissue and body mass traits and to determine whether these QTL interact with the MM locus or with sex. We detected 3 VWR QTL, representing the first voluntary exercise QTL mapped using this high running selection line, and 5 tissue mass QTL. Several interactions between trait QTL and the MM locus as well as sex were also identified. These results begin to explain the genetic architecture of VWR and further support MM as a locus having major effects, includingits main effects on the muscle phenotype, its pleiotropic effects on wheel running and tissue mass traits, and through its interactions with other QTL and with sex.

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“…Several studies in mice have identified quantitative trait loci (QTLs) that influence various obesity related traits. For example, QTLs have been identified for regional adiposity [6], diet induced obesity [7], resistance to diet induced obesity [8], juvenile obesity [9], obesity associated diseases [10,11] as well as lipid content in the liver [12]. …”

Section: Introductionmentioning

confidence: 99%

“…The dissection of fat depots [6], dual energy X-ray absorptiometry (DEXA) [13,14], or magnetic resonance imaging (MRI) [9,13] have been used to measure fat pad size and body fat distribution. Chromatographic techniques (gas chromatography, HPLC) [13], different biochemical reagent sets [8], or enzymatic assays [10] are used for metabolic profiling to obtain information about specific components such as cholesterol, triglycerides, glycerol and others.…”

Section: Introductionmentioning

confidence: 99%

ATR-FTIR spectroscopy reveals genomic loci regulating the tissue response in high fat diet fed BXD recombinant inbred mouse strains

et al. 2013

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BackgroundObesity-associated organ-specific pathological states can be ensued from the dysregulation of the functions of the adipose tissues, liver and muscle. However, the influence of genetic differences underlying gross-compositional differences in these tissues is largely unknown. In the present study, the analytical method of ATR-FTIR spectroscopy has been combined with a genetic approach to identify genetic differences responsible for phenotypic alterations in adipose, liver and muscle tissues.ResultsMice from 29 BXD recombinant inbred mouse strains were put on high fat diet and gross-compositional changes in adipose, liver and muscle tissues were measured by ATR-FTIR spectroscopy. The analysis of genotype-phenotype correlations revealed significant quantitative trait loci (QTL) on chromosome 12 for the content of fat and collagen, collagen integrity, and the lipid to protein ratio in adipose tissue and on chromosome 17 for lipid to protein ratio in liver. Using gene expression and sequence information, we suggest Rsad2 (viperin) and Colec11 (collectin-11) on chromosome 12 as potential quantitative trait candidate genes. Rsad2 may act as a modulator of lipid droplet contents and lipid biosynthesis; Colec11 might play a role in apoptopic cell clearance and maintenance of adipose tissue. An increased level of Rsad2 transcripts in adipose tissue of DBA/2J compared to C57BL/6J mice suggests a cis-acting genetic variant leading to differential gene activation.ConclusionThe results demonstrate that the analytical method of ATR-FTIR spectroscopy effectively contributed to decompose the macromolecular composition of tissues that accumulate fat and to link this information with genetic determinants. The candidate genes in the QTL regions may contribute to obesity-related diseases in humans, in particular if the results can be verified in a bigger BXD cohort.

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Quantitative Trait Loci for Regional Adiposity in Mouse Lines Divergently Selected for Food Intake

Cited by 6 publications

References 69 publications

Genetic variance contributes to dopamine and opioid receptor antagonist-induced inhibition of intralipid (fat) intake in inbred and outbred mouse strains

Genetic variance contributes to dopamine and opioid receptor antagonist-induced inhibition of intralipid (fat) intake in inbred and outbred mouse strains

QTL Underlying Voluntary Exercise in Mice: Interactions with the "Mini Muscle" Locus and Sex

ATR-FTIR spectroscopy reveals genomic loci regulating the tissue response in high fat diet fed BXD recombinant inbred mouse strains

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