Overnight, glucose-stimulated, and fructose-stimulated DNL in control subjects and subjects with NAFLD. Subjects with NAFLD have hepatic (A), adipose tissue (B), and peripheral (C) insulin resistance (n = 14–16 per group). Overnight DNL is increased in insulin-resistant subjects with NAFLD (n = 14 per group) (D). Oral glucose ingestion produces robust plasma glucose (E) and insulin (F) responses, does not stimulate DNL at 240 min in insulin-resistant subjects with NAFLD (G), and is not associated with increases in circulating triglycerides (H) (n = 8 per group). Oral fructose ingestion produces minimal glucose (I) and insulin (J) responses, stimulates DNL at 240 min in both control subjects and subjects with NAFLD (K), and increases circulating triglycerides (L) (n = 6–8 per group). Data are mean ± SEM. *P < 0.05, **P < 0.01 by t test; AP < 0.05 vs. overnight DNL or basal by paired t test. ins. sens., insulin sensitivity.