Diets high in carbohydrates are associated with type 2 diabetes and its comorbidities, including hyperglycemia, hyperlipidemia, obesity, hepatic steatosis and cardiovascular disease. We use a high-sugar diet to study the pathophysiology of diet-induced metabolic disease in Drosophila melanogaster. High-sugar diets produce hyperglycemia, obesity, insulin resistance, and cardiomyopathy in flies along with ectopic accumulation of toxic lipids, or lipotoxicity. Stearoyl-CoA desaturase 1 is an enzyme that contributes to long-chain fatty acid metabolism by introducing a double bond into the acyl chain. Knockdown of stearoyl-CoA desaturase 1 in the fat body reduced lipogenesis and exacerbated pathophysiology in flies reared on high-sugar diets. These flies exhibited dyslipidemia and growth deficiency in addition to defects in cardiac and gut function. We assessed the lipidome of these flies using tandem mass spectrometry to provide insight into the relationship between potentially lipotoxic species and type 2 diabetes-like pathophysiology. Oleic acid supplementation is able to rescue a variety of phenotypes produced by stearoyl-CoA desaturase 1 RNAi, including fly weight, triglyceride storage, gut development, and cardiac failure. Taken together, these data suggest a protective role for monounsaturated fatty acids in diet-induced metabolic disease phenotypes.

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