Dataset Information

A stratified transcriptomics analysis of polygenic fat and lean mouse adipose tissues identifies novel candidate obesity genes.

ABSTRACT: BACKGROUND: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. RESULTS: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. CONCLUSIONS:A focussed candidate gene enrichment strategy in the unique F and L model has identified novel adipose tissue-enriched genes contributing to obesity.

SUBMITTER: Morton NM

PROVIDER: S-EPMC3168488 | biostudies-literature | 2011

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

A stratified transcriptomics analysis of polygenic fat and lean mouse adipose tissues identifies novel candidate obesity genes.

Morton Nicholas M NM Nelson Yvonne B YB Michailidou Zoi Z Di Rollo Emma M EM Ramage Lynne L Hadoke Patrick W F PW Seckl Jonathan R JR Bunger Lutz L Horvat Simon S Kenyon Christopher J CJ Dunbar Donald R DR

PloS one 20110907 9

<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) m ...[more]

PMID: 21915269

Similar Datasets

Project description:Analysis of gene expression profiles of epididymal fat from DIO rats; We applied a comparative functional genomics approach to evaluate diet-induced obese (DIO) rats as an obesity model Experiment Overall Design: Gene expression profiles from DIO and lean rats were generated and compared. A private colony of male Long-Evans rats was set up at Harlan (Harlan-Sprague Dawley, Indianapolis, IN). The animals had been on either a high fat/high sucrose diet (TD95217, Harlan Takled, Madison, WI) or a regular chow (Purina 5008; Ralston-Purina, St. Louis, MO) since weaning. Rats were shipped at 14-weeks of age to our facility and maintained on a 12:12-hour light-dark photoperiod (light on 10:00 PM). They were individually housed throughout the study at ambient temperature, and had free access to diets and water. After 2 weeks acclimation to the facility, body weight of the rats and weight of food consumed in the last 7 days were measured once a week. Body fat mass was analyzed by nuclear magnetic resonance (NMR) using an Echo Medical System (Houston, TX) instrument 3 times throughout the study. Fat free mass is the difference between body mass and fat mass. All animal studies were conducted in compliance with approved institutional animal care and use protocols according to NIH guidelines (NIH publication No. 86-23, 1985). OGTT was conducted after an overnight fasting when animals were 21 weeks of age. After a baseline blood collection (time 0), animals were dosed orally with 1.5 gram/kg glucose. Subsequence blood samples were collected at 30, 60, and 120 minutes post glucose challenge for the determination of plasma glucose and insulin levels. At 25 weeks of age, blood was collected by tail bleeding after overnight fasting. Rats were killed a week later at 09:00am by rapid decapitation. Trunk blood was collected and epididymal fat tissue excised. Various circulating metabolic parameters were measured under fasted (week 25) and fed conditions (week 26). Total RNA from rat epididymal fat was isolated with RNA STAT-60 (Tel-Test) according to the manufacturer's protocol. 5 micrograms of total RNA were labeled and hybridized to Affymetrix RAE230_2 arrays according to the Affymetrix protocol.

Dataset Information

A stratified transcriptomics analysis of polygenic fat and lean mouse adipose tissues identifies novel candidate obesity genes.

Publications

A stratified transcriptomics analysis of polygenic fat and lean mouse adipose tissues identifies novel candidate obesity genes.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets