The optimum amounts of macronutrients in human diets is currently a subject of great interest. Diets emphasizing fat restriction, low carbohydrates or high protein content are promoted in popular books, but little is known about their long-term metabolic effects. We found that various E. coli strains commonly used to maintain C. elegans in most laboratory studies have distinct nutrient compositions. Nematodes maintained on these strains show significant differences in lifespan, fat storage, and feeding behavior. While all E. coli strains have a relatively high protein content, carbohydrate content varies in strains depending on whether or not they secrete a polysaccharide capsule. When growing on the capsule-secreting strain HB101, we found that wild type C. elegans show increased quiescence, reduced fat stores, and a shorter lifespan compared to C. elegans growing on the capsule-less strain OP50. Gene expression studies indicate an increase in fat metabolism in C. elegans growing on OP50, which may induce mitochondrial metabolism and a hormetic response that enables an extended lifespan. We find that the differences lifespan among worms grown on the two bacterial strains depends on efficient feeding, since
eat-2 mutants show equally extended lifespans on both bacterial strains. We also find that AAK-2, a homolog of the large subunit of AMP-dependent kinase (AMPK), is necessary for the increased lifespan on OP50. Fat storage depends on feeding, since
eat-2 shows indistinguishable low fat stores on both bacterial strains. Furthermore, mutants in the peptide transporter encoded by
opt-2 store equally high amounts of fat when growing on both bacterial strains. Our studies indicate that various nutrient sensing pathways feed back to influence feeding behavior and metabolism, which in turn affect fat storage and lifespan.