Intramyocellular Fatty Acid Trafficking in Insulin Resistance States - Effects of Intestinal Delivery of Lipids

Muscle insulin resistance is a hallmark of upper body obesity (UBO) and Type 2 diabetes
(T2DM). It is unknown whether muscle free fatty acid (FFA) availability or intramyocellular
fatty acid trafficking is responsible for muscle insulin resistance, although it has been
shown that raising FFA with Intralipid can cause muscle insulin resistance within 4 hours.
The investigators do not understand to what extent the incorporation of FFA into ceramides or
diacylglycerols (DG) affect insulin signaling and muscle glucose uptake. The investigators
propose to alter the profile and concentrations of FFA of healthy, non-obese adults using an
overnight, intra-duodenal palm oil infusion vs. an overnight intra-duodenal Intralipid
infusion (both compared to saline control). The investigators will compare the muscle FFA
storage into intramyocellular triglyceride, intramyocellular fatty acid trafficking,
activation of the insulin signaling pathway and glucose disposal rates, providing the first
measure of how different FFA profiles alter muscle FFA trafficking and insulin action at the
whole body and cellular/molecular levels. By identifying which steps in the insulin signaling
pathway are most affected, the investigators will determine the site-specific effect of
ceramides and/or DG on different degrees of insulin resistance.

Hypothesis 1: Palm oil infusion will result in abnormal FFA trafficking into
intra-myocellular ceramides and abnormal insulin signaling.

Hypothesis 2: Intralipid infusion will result in abnormal FFA trafficking into
intra-myocellular saturated DG and abnormal insulin signaling.