Relationship between obesity phenotypes and genetic determinants in a mouse model for juvenile obesity

Gudrun A. Brockmann, Nadine Schäfer, Claudia Hesse, Sebastian Heise, Christina Neuschl, Asja Wagener, Gary A. Churchill, Renhua Li

Research output: Contribution to journalArticlepeer-review

2 Scopus citations


Obesity, a state of imbalance between lean mass and fat mass, is important for the etiology of diseases affected by the interplay of multiple genetic and environmental factors. Although genome-wide association studies have repeatedly associated genes with obesity and body weight, the mechanisms underlying the interaction between the muscle and adipose tissues remain unknown. Using 351 mice (at 10 wk of age) of an intercross population between Berlin Fat Mouse Inbred (BFMI) and C57BL/6NCrl (B6N) mice, we examined the causal relationships between genetic variations and multiple traits: body lean mass and fat mass, adipokines, and bone mineral density. Furthermore, evidence from structural equation modeling suggests causality among these traits. In the BFMI model, juvenile obesity affects lean mass and impairs bone mineral density via adipokines secreted from the white adipose tissues. While previous studies have indicated that lean mass has a causative effect on adiposity, in the Berlin Fat Mouse model that has been selected for juvenile obesity (at 9 wk of age) for >90 generations, however, the causality is switched from fat mass to lean mass. In addition, linkage studies and statistical modeling have indicated that quantitative trait loci on chromosomes 5 and 6 affect both lean mass and fat mass. These lines of evidence indicate that the muscle and adipose tissues interact with one another and the interaction is modulated by genetic variations that are shaped by selections. Experimental examinations are necessary to verify the biological role of the inferred causalities.

Original languageEnglish
Pages (from-to)817-826
Number of pages10
JournalPhysiological Genomics
Issue number18
StatePublished - 15 Sep 2013
Externally publishedYes


  • Adiponectin
  • Bone mineral density
  • Lean and fat mass
  • Leptin
  • Networks


Dive into the research topics of 'Relationship between obesity phenotypes and genetic determinants in a mouse model for juvenile obesity'. Together they form a unique fingerprint.

Cite this