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

Summary

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.

Conditions

• Insulin Resistance

Interventions

DIETARY_SUPPLEMENT

Intralipid

Half of the participants will receive either naso-duodenal infusion of intralipid or palm oil each participant will serve as their own saline control on the second study day.

DIETARY_SUPPLEMENT

Palm Oil Emulsion

Half of the participants will receive either naso-duodenal infusion of intralipid or palm oil each participant will serve as their own saline control on the second study day.

OTHER

Saline

All participants will serve as their own controls with a saline infusion study day.

Sponsors & Collaborators

• National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)

  collaborator NIH

• Mayo Clinic

  lead OTHER

Principal Investigators

• Michael D Jensen, MD · Mayo Clinic

Study Design

Allocation

RANDOMIZED

Purpose

BASIC_SCIENCE

Masking

NONE

Model

PARALLEL

Eligibility

Min Age

18 Years

Max Age

55 Years

Sex

ALL

Healthy Volunteers

Yes

Timeline & Regulatory

Start

2018-12-01

Primary Completion

2026-12-31

Completion

2026-12-31

Countries

• United States

Study Locations