Because available food resources vary among habitats, animals colonizing nutrient-poor environments should increase the ability to absorb or retain nutrients. The thrifty gene hypothesis, which has been proposed to explain metabolic diseases in modern human society, posits that genotypes that help organisms survive in nutrient-poor situations may become detrimental in nutrient-rich situations. If this is the case with natural populations, animal populations adapted to nutrient-poor environments may show abnormalities similar to human metabolic diseases if they are brought to nutrient-rich situations. Here, we tested the thrifty gene hypothesis using the three-spined stickleback fish (Gasterosteus aculeatus).
    The three-spined stickleback fish are widely distributed in the temperate northern hemisphere. The marine ancestors independently colonized freshwater environments multiple times worldwide. The availability of nutrients greatly varies among habitats. Generally, the marine environment is nutrition-rich, while the freshwater environment is nutrition-poor. Thus, freshwater stickleback populations might evolve genotypes to cope with a nutrition-poor situation during freshwater adaptation. Can the freshwater genotype benefit sticklebacks to survive in a poor nutrition environment? Can that ability become an obstacle to moving back to the marine environment?
    To answer these questions, we conducted a feeding experiment. Freshwater and marine ecotypes were fed nutrient-poor and nutrient-rich diets. Two months after fertilization, we investigated the accumulation of visceral fat, body size, and blood cholesterol level. For a subset of fish, we also conducted whole body lipidome, whole body metabolome, and liver transcriptome analyses.
    First, we found that the freshwater ecotype accumulated more fat in their visceral cavity and had higher blood cholesterol levels when fed with nutrient-rich diets compared with nutrient-poor diets. In contrast, the marine ecotype did not change these traits by the diets. Second, lipidome and metabolome analyses revealed that freshwater and marine ecotypes have different strategies to utilize lipids. Under the rich nutrition condition, beta-oxidation, which converts fatty acids to energy, was activated in the marine ecotype. In contrast, the freshwater ecotype tended to store the food-derived lipids as a triglyceride in the visceral cavity rather than using them for energy production. Finally, RNA-seq data of the liver also supported these findings. In conclusion, freshwater ecotype showed symptoms similar to human metabolic diseases when fed with nutrient-rich diets, which supports the thrifty gene hypothesis.