Abstract
The Berlin Fat Mouse Inbred (BFMI) line harbors a major recessive gene defect on chromosome 3 (jobes1) leading to juvenile obesity and metabolic syndrome. The present study aimed at the identification of metabolites that might be linked to recessively acting genes in the obesity locus. Firstly, serum metabolites were analyzed between obese BFMI and lean B6 and BFMI × B6 F1 mice to identify metabolites that are different. In a second step, a metabolite–protein network analysis was performed linking metabolites typical for BFMI mice with genes of the jobes1 region. The levels of 22 diacyl-phosphatidylcholines (PC aa), two lyso-PC and three carnitines were found to be significantly lower in obese mice compared with lean mice, while serine, glycine, arginine and hydroxysphingomyelin were higher for the same comparison. The network analysis identified PC aa C42:1 as functionally linked with the genes Ccna2 and Trpc3 via the enzymes choline kinase alpha and phospholipase A2 group 1B (PLA2G1B), respectively. Gene expression analysis revealed elevated Ccna2 expression in adipose tissue of BFMI mice. Furthermore, unique mutations were found in the Ccna2 promoter of BFMI mice which are located in binding sites for transcription factors or micro RNAs and could cause differential Ccna2 mRNA levels between BFMI and B6 mice. Increased expression of Ccna2 was consistent with higher mitotic activity of adipose tissue in BFMI mice. Therefore, we suggest a higher demand for PC necessary for adipose tissue growth and remodeling. This study highlights the relationship between metabolite profiles and the underlying genetics of obesity in the BFMI line.Electronic supplementary materialThe online version of this article (doi:10.1007/s11306-013-0590-1) contains supplementary material, which is available to authorized users.
Highlights
The Berlin Fat Mouse Inbred (BFMI) line harbors a major recessive gene defect on chromosome 3 leading to juvenile obesity and metabolic syndrome
Unique mutations were found in the Ccna2 promoter of BFMI mice which are located in binding sites for transcription factors or micro RNAs and could cause differential Ccna2 mRNA levels between BFMI and BFMI C57BL/6NCrl (B6) mice
Due to the recessive jObes1 effect in BFMI mice leading to obesity (Neuschl et al 2010) BFMI males showed 3.1- and 2.2-fold and females 3.0- and 2.8-fold higher body fat content at 10 weeks compared with its B6 and F1 counterparts (p \ 0.001), respectively (Table 1)
Summary
The Berlin Fat Mouse Inbred (BFMI) line harbors a major recessive gene defect on chromosome 3 (jobes1) leading to juvenile obesity and metabolic syndrome. The present study aimed at the identification of metabolites that might be linked to recessively acting genes in the obesity locus. A metabolite–protein network analysis was performed linking metabolites typical for BFMI mice with genes of the jobes region. Gene expression analysis revealed elevated Ccna expression in adipose tissue of BFMI mice. Increased expression of Ccna was consistent with higher mitotic activity of adipose tissue in BFMI mice. This study highlights the relationship between metabolite profiles and the underlying genetics of obesity in the BFMI line. J. Adamski Institute of Experimental Genetics, Genome Analysis Center, Helmholtz Zentrum Munchen, Ingolstadter Landstr. A new approach for biomarker identification is the metabolomics (Shaham et al 2008; Shah et al 2010; Wang-Sattler et al 2012)
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
