Assessment of diet-induced obese rats as an obesity model by comparative functional genomics.
OBJECTIVE
We applied a comparative functional genomics approach to evaluate whether diet-induced obese (DIO) rats serve as an effective obesity model.


METHODS
Gene-expression profiles of epididymal fat from DIO and lean rats were generated using microarrays and compared with the published array data of obese and non-obese human subcutaneous adipocytes.


RESULTS
Caloric intake and fuel efficiency were significantly higher in DIO rats, which resulted in increased body weight and adiposity. Circulating glucose, cholesterol, triglyceride, insulin, and leptin levels in DIO rats were significantly higher than those in the lean controls. DIO rats also exhibited impaired insulin sensitivity. A direct comparison of gene-expression profiles from DIO and lean rats and those from obese and non-obese humans revealed that global gene-expression patterns in DIO rat fat resemble those of obese human adipocytes. Differentially expressed genes between obese and non-obese subjects in both human and rat studies were identified and associated with biological pathways by mapping genes to Gene Ontology (GO) categories. Immune response-related genes and angiogenesis-related genes exhibited significant upregulation in both obese humans and DIO rats when compared with non-obese controls. However, genes in fatty acid metabolism and oxidation exhibited a broad downregulation only in obese human adipocytes but not in DIO rat epididymal fat.


CONCLUSIONS
Our study based on gene-expression profiling suggested that DIO rats in general represent an appropriate obesity model. However, the discrepancies in gene-expression alterations between DIO rats and obese humans, particularly in the metabolic pathways, may explain the limitations of using DIO rodent models in obesity research and drug discovery.
Li
Shuyu
S
Integrative Biology, Lilly Research Laboratories, Eli Lilly and Company, Lilly Corporate Center, Indianapolis, Indiana, USA.
Zhang
Hong-Yan
HY
Hu
Charlie C
CC
Lawrence
Frank
F
Gallagher
Kelly E
KE
Surapaneni
Anupama
A
Estrem
Shawn T
ST
Calley
John N
JN
Varga
Gabor
G
Dow
Ernst R
ER
Chen
Yanyun
Y
D017667:Adipocytes / Q000166:cytology / Q000502:physiology; D000821:Animal Feed; D000818:Animals; D001823:Body Composition / Q000235:genetics; D001835:Body Weight / Q000235:genetics; D002478:Cells, Cultured; D004041:Dietary Fats / Q000494:pharmacology*; D019422:Dietary Sucrose / Q000494:pharmacology*; D004195:Disease Models, Animal; D004435:Eating / Q000235:genetics; D020869:Gene Expression Profiling; D020022:Genetic Predisposition to Disease; D023281:Genomics; D006801:Humans; D007198:Indians, North American; D007333:Insulin Resistance / Q000235:genetics; D008297:Male; D009765:Obesity / Q000209:etiology / Q000235:genetics* / Q000378:metabolism; D020411:Oligonucleotide Array Sequence Analysis; D051381:Rats; D020318:Rats, Long-Evans
D004041:Dietary Fats; D019422:Dietary Sucrose