Overview
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.
Eligibility
Inclusion Criteria:
- Women and Men (Women premenopausal)
- BMI 18-27
- Weight stable
- Not pregnant/nursing
Exclusion Criteria:
- Ischemic heart disease
- Atherosclerotic valvular disease
- Smokers (> 20 cigarettes per week)
- Bilateral oophorectomy
- Concomitant use of medications that can alter serum lipid profile (high dose fish oil, statins, niacin, fibrates, thiazolinediones, beta-blockers, atypical antipsychotics)
- Lidocaine allergy