In this study, we report that enhanced S100A9 in ID mice exerts several beneficial metabolic effects (e.g., it normalizes the hyperketonemia, hypertriglyceridemia, and increased hepatic fatty acid oxidation (FAO) caused by β-cell loss) and extends their lifespan, at least in part, through TLR4 (while other contributing mechanism cannot be ruled out at this stage). The gene discussed is S100A9; the disease is hypertriglyceridemia.