Mechanisms of population level variation in fatness and leanness

Abstract

Obesity represents the extreme of fat deposition. Adipose tissue from many obese models has been well‐characterized. However, much less is known about differences in adipose tissue between leaner and fattier individuals within a population. The objective of this study was to determine if fatness can be attributed to changes in expression of key lipogenic and adipogenic genes, in the context of a heterogeneous genetic background. The C57BL/6J * DBA/2J (BXD) recombinant inbred mouse strain panel was used to select 2 mice each from 6 lean and 6 fatty strains, based on percent abdominal fat. Expression of adipogenic and lipogenic genes were profiled using PCR Arrays (sabiosciences.com). Using Pearson's correlation genes correlated with adiposity were identified, and Student's t‐test was used to identify differentially expressed genes between lean and fatty mice. Ten of the 84 genes measured differed significantly between groups (p<0.05) including expected genes such as leptin and adipsin as well. Other genes less characterized with regard to fatness also differed between groups, including Cdkn1a and Mapk14 (p<0.05). Significant correlations were identified among adipokines and adipogenic genes independent of fatness, suggesting concerted regulation of adipogenic and endocrine functions. These data highlight pathways that alter adipose tissue composition and function in the absence of overt obesity.