Effect of Dietary SFA and Fructose on Hepatic Insulin Sensitivity

High rates of de novo lipogenesis (DNL) and high saturated fatty acid (SFA) fraction in the liver both have been associated with poor metabolic health and hepatic insulin resistance. Interestingly, the end product of DNL is mainly SFA. So far it is unknown whether it is the process of DNL or the accumulation of SFA per se that leads to hepatic insulin resistance. Therefore, it is of interest to compare the effect of a diet that modifies directly hepatic SFA content (4-week high SFA diet) and a diet that changes SFA indirectly by modifying rates of DNL (4-week high fructose diet). To this end, 18 overweight/obese, but otherwise healthy, males and females will take part in the randomized dietary interventions. The primary outcome is hepatic insulin sensitivity (suppression of EGP during clamp) upon a 4-week high SFA diet versus a 4-week fructose diet.