Here in this study, we evaluated the influence of removing the gut microbiota on muscle physiology in wildtype Canton‐S (CS) and in obese Drosophila models (induced by a HFD or predisposed obesity mutant Sk2) by measuring muscle performance, ATP production, insulin resistance, glucose levels, and ectopic lipid deposition. Here, SPHK2 is linked to obesity due to melanocortin 4 receptor deficiency.