Obesity in BSB mice is correlated with expression of genes for iron homeostasis and leptin.
OBJECTIVE
We searched for genes whose alleles cause obesity and novel pathways correlated with obesity.


METHODS
BSB mice are a model of complex obesity due to interactions among genes from C57BL/6J (B) and Mus spretus (SPRET) in (B x SPRET) x B backcross mice. Stringent criteria identified 50 genes differentially expressed in epididymal adipose tissue from 7 pairs of lean vs. obese BSB mice. Quantitative reverse transcription-polymerase chain reaction of adipose tissue RNA from 48 BSB mice with a range of obesity was assayed. Leptin was evaluated in inbred (SPRET/Ei) and outbred (SPRET/Pt) BSB mice.


RESULTS
Leptin (Lep) and adipsin expressions had the greatest fold differences between obese and lean mice. Four genes involved in iron homeostasis were included in the 50 differentially expressed genes [hemochromatosis (Hfe), diaphorase 1, transferrin receptor (Trfr) 2, and protoporphyrinogen oxidase] and two additional iron-related genes did not quite meet the stringent criteria for differential expression (Trfr and lactotransferrin). Hfe and Trfr mRNA levels and liver iron were negatively correlated with fat mass. Variation in obesity phenotypes explained 49%, 40%, and 37%, respectively, of the variance in Hfe, Lep, and Trfr mRNA levels. Leptin differed by haplotype at the Lep locus in outbred BSB. The quantitative trait locus identified in the outbred cross did not occur in inbred BSB.


CONCLUSIONS
Our results suggest that iron homeostasis in BSB mice is coordinately regulated in vivo in adipose depots in response to obesity. Lep alleles derived from outbred, but not inbred, SPRET are a positional candidate for the chromosome 6 quantitative trait locus in BSB mice.
Rowe Program in Genetics, University of California, Davis, California 95616, USA.
Poupak
P
Farahani
Sally
S
Chiu
Christopher L
CL
Bowlus
Dario
D
Boffelli
Eric
E
Lee
Janis S
JS
Fisler
Ronald M
RM
Krauss
Craig H
CH
Warden
D000483:Alleles; D000704:Analysis of Variance; D000818:Animals; D003433:Crosses, Genetic; D004195:Disease Models, Animal; D005260:Female; D020869:Gene Expression Profiling; D014644:Genetic Variation; D006706:Homeostasis; D007501:Iron / Q000378:metabolism*; D020738:Leptin / Q000235:genetics / Q000378:metabolism*; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D009765:Obesity / Q000235:genetics* / Q000378:metabolism; D020411:Oligonucleotide Array Sequence Analysis; D040641:Quantitative Trait Loci; D020133:Reverse Transcriptase Polymerase Chain Reaction
D020738:Leptin; D007501:Iron