A stratified transcriptomics analysis of polygenic fat and lean mouse adipose tissues identifies novel candidate obesity genes.
<h4>Background</h4>Obesity and metabolic syndrome results from a complex interaction between genetic and environmental factors. In addition to brain-regulated processes, recent genome wide association studies have indicated that genes highly expressed in adipose tissue affect the distrib...
Saved in:
| Main Authors: | , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Public Library of Science (PLoS)
2011-01-01
|
| Series: | PLoS ONE |
| Online Access: | https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0023944&type=printable |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1849470523780628480 |
|---|---|
| author | Nicholas M Morton Yvonne B Nelson Zoi Michailidou Emma M Di Rollo Lynne Ramage Patrick W F Hadoke Jonathan R Seckl Lutz Bunger Simon Horvat Christopher J Kenyon Donald R Dunbar |
| author_facet | Nicholas M Morton Yvonne B Nelson Zoi Michailidou Emma M Di Rollo Lynne Ramage Patrick W F Hadoke Jonathan R Seckl Lutz Bunger Simon Horvat Christopher J Kenyon Donald R Dunbar |
| author_sort | Nicholas M Morton |
| collection | DOAJ |
| description | <h4>Background</h4>Obesity and metabolic syndrome results from a complex interaction between genetic and environmental factors. In addition to brain-regulated processes, recent genome wide association studies have indicated that genes highly expressed in adipose tissue affect the distribution and function of fat and thus contribute to obesity. Using a stratified transcriptome gene enrichment approach we attempted to identify adipose tissue-specific obesity genes in the unique polygenic Fat (F) mouse strain generated by selective breeding over 60 generations for divergent adiposity from a comparator Lean (L) strain.<h4>Results</h4>To enrich for adipose tissue obesity genes a 'snap-shot' pooled-sample transcriptome comparison of key fat depots and non adipose tissues (muscle, liver, kidney) was performed. Known obesity quantitative trait loci (QTL) information for the model allowed us to further filter genes for increased likelihood of being causal or secondary for obesity. This successfully identified several genes previously linked to obesity (C1qr1, and Np3r) as positional QTL candidate genes elevated specifically in F line adipose tissue. A number of novel obesity candidate genes were also identified (Thbs1, Ppp1r3d, Tmepai, Trp53inp2, Ttc7b, Tuba1a, Fgf13, Fmr) that have inferred roles in fat cell function. Quantitative microarray analysis was then applied to the most phenotypically divergent adipose depot after exaggerating F and L strain differences with chronic high fat feeding which revealed a distinct gene expression profile of line, fat depot and diet-responsive inflammatory, angiogenic and metabolic pathways. Selected candidate genes Npr3 and Thbs1, as well as Gys2, a non-QTL gene that otherwise passed our enrichment criteria were characterised, revealing novel functional effects consistent with a contribution to obesity.<h4>Conclusions</h4>A focussed candidate gene enrichment strategy in the unique F and L model has identified novel adipose tissue-enriched genes contributing to obesity. |
| format | Article |
| id | doaj-art-beb69d9e6dde4131b90e2f3a8bdbed1f |
| institution | Kabale University |
| issn | 1932-6203 |
| language | English |
| publishDate | 2011-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj-art-beb69d9e6dde4131b90e2f3a8bdbed1f2025-08-20T03:25:08ZengPublic Library of Science (PLoS)PLoS ONE1932-62032011-01-0169e2394410.1371/journal.pone.0023944A stratified transcriptomics analysis of polygenic fat and lean mouse adipose tissues identifies novel candidate obesity genes.Nicholas M MortonYvonne B NelsonZoi MichailidouEmma M Di RolloLynne RamagePatrick W F HadokeJonathan R SecklLutz BungerSimon HorvatChristopher J KenyonDonald R Dunbar<h4>Background</h4>Obesity and metabolic syndrome results from a complex interaction between genetic and environmental factors. In addition to brain-regulated processes, recent genome wide association studies have indicated that genes highly expressed in adipose tissue affect the distribution and function of fat and thus contribute to obesity. Using a stratified transcriptome gene enrichment approach we attempted to identify adipose tissue-specific obesity genes in the unique polygenic Fat (F) mouse strain generated by selective breeding over 60 generations for divergent adiposity from a comparator Lean (L) strain.<h4>Results</h4>To enrich for adipose tissue obesity genes a 'snap-shot' pooled-sample transcriptome comparison of key fat depots and non adipose tissues (muscle, liver, kidney) was performed. Known obesity quantitative trait loci (QTL) information for the model allowed us to further filter genes for increased likelihood of being causal or secondary for obesity. This successfully identified several genes previously linked to obesity (C1qr1, and Np3r) as positional QTL candidate genes elevated specifically in F line adipose tissue. A number of novel obesity candidate genes were also identified (Thbs1, Ppp1r3d, Tmepai, Trp53inp2, Ttc7b, Tuba1a, Fgf13, Fmr) that have inferred roles in fat cell function. Quantitative microarray analysis was then applied to the most phenotypically divergent adipose depot after exaggerating F and L strain differences with chronic high fat feeding which revealed a distinct gene expression profile of line, fat depot and diet-responsive inflammatory, angiogenic and metabolic pathways. Selected candidate genes Npr3 and Thbs1, as well as Gys2, a non-QTL gene that otherwise passed our enrichment criteria were characterised, revealing novel functional effects consistent with a contribution to obesity.<h4>Conclusions</h4>A focussed candidate gene enrichment strategy in the unique F and L model has identified novel adipose tissue-enriched genes contributing to obesity.https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0023944&type=printable |
| spellingShingle | Nicholas M Morton Yvonne B Nelson Zoi Michailidou Emma M Di Rollo Lynne Ramage Patrick W F Hadoke Jonathan R Seckl Lutz Bunger Simon Horvat Christopher J Kenyon Donald R Dunbar A stratified transcriptomics analysis of polygenic fat and lean mouse adipose tissues identifies novel candidate obesity genes. PLoS ONE |
| title | A stratified transcriptomics analysis of polygenic fat and lean mouse adipose tissues identifies novel candidate obesity genes. |
| title_full | A stratified transcriptomics analysis of polygenic fat and lean mouse adipose tissues identifies novel candidate obesity genes. |
| title_fullStr | A stratified transcriptomics analysis of polygenic fat and lean mouse adipose tissues identifies novel candidate obesity genes. |
| title_full_unstemmed | A stratified transcriptomics analysis of polygenic fat and lean mouse adipose tissues identifies novel candidate obesity genes. |
| title_short | A stratified transcriptomics analysis of polygenic fat and lean mouse adipose tissues identifies novel candidate obesity genes. |
| title_sort | stratified transcriptomics analysis of polygenic fat and lean mouse adipose tissues identifies novel candidate obesity genes |
| url | https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0023944&type=printable |
| work_keys_str_mv | AT nicholasmmorton astratifiedtranscriptomicsanalysisofpolygenicfatandleanmouseadiposetissuesidentifiesnovelcandidateobesitygenes AT yvonnebnelson astratifiedtranscriptomicsanalysisofpolygenicfatandleanmouseadiposetissuesidentifiesnovelcandidateobesitygenes AT zoimichailidou astratifiedtranscriptomicsanalysisofpolygenicfatandleanmouseadiposetissuesidentifiesnovelcandidateobesitygenes AT emmamdirollo astratifiedtranscriptomicsanalysisofpolygenicfatandleanmouseadiposetissuesidentifiesnovelcandidateobesitygenes AT lynneramage astratifiedtranscriptomicsanalysisofpolygenicfatandleanmouseadiposetissuesidentifiesnovelcandidateobesitygenes AT patrickwfhadoke astratifiedtranscriptomicsanalysisofpolygenicfatandleanmouseadiposetissuesidentifiesnovelcandidateobesitygenes AT jonathanrseckl astratifiedtranscriptomicsanalysisofpolygenicfatandleanmouseadiposetissuesidentifiesnovelcandidateobesitygenes AT lutzbunger astratifiedtranscriptomicsanalysisofpolygenicfatandleanmouseadiposetissuesidentifiesnovelcandidateobesitygenes AT simonhorvat astratifiedtranscriptomicsanalysisofpolygenicfatandleanmouseadiposetissuesidentifiesnovelcandidateobesitygenes AT christopherjkenyon astratifiedtranscriptomicsanalysisofpolygenicfatandleanmouseadiposetissuesidentifiesnovelcandidateobesitygenes AT donaldrdunbar astratifiedtranscriptomicsanalysisofpolygenicfatandleanmouseadiposetissuesidentifiesnovelcandidateobesitygenes AT nicholasmmorton stratifiedtranscriptomicsanalysisofpolygenicfatandleanmouseadiposetissuesidentifiesnovelcandidateobesitygenes AT yvonnebnelson stratifiedtranscriptomicsanalysisofpolygenicfatandleanmouseadiposetissuesidentifiesnovelcandidateobesitygenes AT zoimichailidou stratifiedtranscriptomicsanalysisofpolygenicfatandleanmouseadiposetissuesidentifiesnovelcandidateobesitygenes AT emmamdirollo stratifiedtranscriptomicsanalysisofpolygenicfatandleanmouseadiposetissuesidentifiesnovelcandidateobesitygenes AT lynneramage stratifiedtranscriptomicsanalysisofpolygenicfatandleanmouseadiposetissuesidentifiesnovelcandidateobesitygenes AT patrickwfhadoke stratifiedtranscriptomicsanalysisofpolygenicfatandleanmouseadiposetissuesidentifiesnovelcandidateobesitygenes AT jonathanrseckl stratifiedtranscriptomicsanalysisofpolygenicfatandleanmouseadiposetissuesidentifiesnovelcandidateobesitygenes AT lutzbunger stratifiedtranscriptomicsanalysisofpolygenicfatandleanmouseadiposetissuesidentifiesnovelcandidateobesitygenes AT simonhorvat stratifiedtranscriptomicsanalysisofpolygenicfatandleanmouseadiposetissuesidentifiesnovelcandidateobesitygenes AT christopherjkenyon stratifiedtranscriptomicsanalysisofpolygenicfatandleanmouseadiposetissuesidentifiesnovelcandidateobesitygenes AT donaldrdunbar stratifiedtranscriptomicsanalysisofpolygenicfatandleanmouseadiposetissuesidentifiesnovelcandidateobesitygenes |