Island colonizing organisms often evolve extreme body sizes. Notable examples of this phenomenon include evolved dwarfism in an extinct insular elephant and hominin, and acquired gigantism in numerous insular rodents. Although the generality of the phenomenon suggests common evolutionary mechanisms, the genetic basis of extreme body size evolution on islands remains poorly understood. A striking case of island gigantism is that observed on Gough Island (GI) where house mice evolved to become the largest wild representatives of their species in just 200 years. To illuminate the genetic basis of metabolic processes contributing to the extreme size of GI mice and to nominate candidate genes involved in gigantism evolution we characterized gene expression evolution in three metabolic organs. A total of 100 RNA-sequencing libraries were constructed for GI mice and a wild-derived strain with size representative of mainland mice (WSB) for five conditions: the liver from embryonic, 2-week, and 4-week old mice, and the gonadal adipose depot and hypothalamus from 4-week old mice. We employed the software package RSEM to align reads and quantify transcripts. Using the R package DESeq2, we detected differential expression between GI and WSB mice at thousands of genes in each condition. The embryonic liver and adipose manifested the most differentially expressed (DE) genes. The adipose exhibited a significant excess of highly expressed genes in large magnitude fold change classes, indicating elevated activity of the pathways constructed by these genes (including metabolically driven cell growth). Monitoring patterns of liver-specific gene expression across three time points enabled grouping of genes with similar temporal expression profiles, shedding light on the evolution of co-regulated genes acting to promote extreme size evolution. In all conditions assayed, we found a significant association between proximal upstream single nucleotide polymorphisms and differential gene expression, suggesting a role for cis-regulatory evolution in GI metabolism. We identified 91 DE genes within +/- 3Mb of QTL for body size recently mapped in crosses between GI and WSB mice. A subset of these genes harbor fixed sequence differences between GI and WSB mice in potential upstream regulatory regions. This study further establishes the GI mouse as a model for understanding the genetic basis of insular body size evolution and provides candidate genes for potential functional genetic assays that explore variable and abnormal growth and metabolism in vertebrates.