Obesity is becoming a global pandemic. It is associated with diabetes, cardiovascular disease, hypertension, and many forms of cancer. Obesity develops when energy intake exceeds energy expenditure, leading to the net accumulation of triglycerides. New breakthroughs have revealed that stearoyl-CoA desaturase (SCD) plays a significant role in energy balance and obesity. In the biosynthesis of fat, SCD is a key enzyme that converts saturated fatty acids to monounsaturated fatty acids, which are the most abundant fatty acids of membrane phospholipids, triglycerides, wax, and cholesterol esters. The C. elegans
fat-6;
fat-7 SCD double mutants, similar to mammalian SCD1 mutants, have reduced fat stores and developmental defects. Likewise, the insulin/IGF-1 signaling pathway is remarkably conserved in worms, flies, and mammals. In C. elegans, the insulin/IGF-1 signaling pathway regulates life span, fat storage, dauer diapause, reproduction, and stress responses. Searches for downstream targets of this pathway identified genes involved in lipid and carbohydrate metabolism. The expression of
fat-7 is upregulated in
daf-2 mutants. These studies raise the questions of whether the regulation of fat storage by the insulin/IGF-1 pathway depends on SCD, and how insulin/IGF-1 signaling pathway and stearoyl-CoA desaturase coordinately or independently regulate growth, stress responses, and even lifespan. To address theses questions, we generated
daf-2;
fat-6;
fat-7 triple mutants. We found that
daf-2;
fat-6;
fat-7 triple mutants accumulate same amount of fat as
daf-2 single mutant by GC/TLC and fixed Nile Red staining. The
daf-2 mutation also suppresses the susceptibility of
fat-6;
fat-7 double mutants to heat and pathogen stress. However, the insulin/IGF-1 signaling pathway and SCD overlap to regulate growth rate and brood size. We are currently investigating target genes that regulate fat stores of
daf-2;
fat-6;
fat-7 triple mutants by quantitative RT-PCR and RNAi. Taken together, these studies will provide insights into the mechanisms of fat accumulation and the development of diabetes and obesity in humans.