Four-and-a-half LIM domain protein 2 (FHL2) deficiency protects mice from diet-induced obesity and high FHL2 expression correlates with obesity in man.

Four-and-a-Half-LIM-domain-protein 2 (FHL2) modulates multiple signal transduction pathways but has not been implicated in obesity or energy metabolism. In man, FHL2 expression increases with age and high FHL2 expression is associated with increased body weight in human and mice, leading us to hypothesize that FHL2 is a determinant of diet-induced obesity. Accordingly, loss of FHL2 protects mice from high-fat diet-induced weight gain. This is associated with enhanced energy expenditure in FHL2-/- mice. In an attempt to discover the origin of the increased energy expenditure in FHL2-/- mice, we performed transcriptome analysis (RNA-seq) on the heart, since FHL2 is highly expressed in this organ and gonadal white adipose tissue in WT and FHL2-/- mice. Overall design: Gene expression profiling by RNA-seq was performed in heart and gonadal white adipose tissue (gWAT) from WT and FHL2-/- mice after 8 weeks of high fat diet.