Fatty Acid Metabolism and Insulin Sensitivity: the Role of Endurance Exercise

Clearly the effects of diet and exercise are beneficial for obese persons, but the underlying mechanisms for the improvements in metabolic health are not completely clear. Although mounting evidence suggests that alterations in lipid metabolism in persons with abdominal obesity are associated with a several medical complications, including diabetes, little is known about the factors responsible for this effect. The project in this application is designed to examine how the addition of endurance exercise training to a weight-loss program alters whole-body fatty acid availability, uptake, and oxidation as well as the expression of cellular factors that regulate these processes. In addition, we will evaluate whether these alterations are associated with improvements in insulin sensitivity. In the end, these experiments will provide insight into the cellular and whole-body adaptations in fatty acid metabolism in response to weight-loss and exercise training that may lead to enhancement of insulin sensitivity. Identifying relationships between gene expression, whole-body fatty acid metabolism and clinical outcome measurements, such as insulin sensitivity, may lead to improvements in the therapeutic and/or the preventative approach to obesity and its co-morbidities.

Study Overview

• Status: Completed
• Conditions: Insulin Resistance and Type 2 Diabetes
• Intervention / Treatment: Behavioral: Weight loss - diet only; Behavioral: Weight loss plus exercise

Detailed Description

Despite robust findings emphasizing the importance of weight-loss and exercise for the prevention and management of insulin resistance and Type 2 diabetes, the mechanisms responsible for the improvements in metabolic health are not completely understood. Mounting evidence suggests that abnormalities in fatty acid metabolism in persons with abdominal obesity are associated with insulin resistance. Alterations in fatty acid mobilization and oxidation may be primary adaptations responsible for the improvements in metabolic health after weight-loss and endurance exercise training. We hypothesize that a disparity between muscle fatty acid uptake and oxidation is regulated by the expression of genes and proteins that participate in intracellular transport, trafficking, and metabolism of fatty acids. We believe that alterations in the expression of these factors in response to weight-loss and endurance exercise training will underlie changes in the non-oxidative disposal of fatty acids, and thereby improve insulin sensitivity. We will determine the effects of weight-loss and exercise training on whole-body fatty acid mobilization and oxidation and the expression of factors that regulate these processes in skeletal muscle. In addition, we will evaluate how these alterations are associated with improvements in insulin sensitivity. These studies will provide insight into how cellular alterations with weight-loss and exercise training and the accompanying changes in whole-body fatty acid metabolism may lead to improvements in metabolic health.

• Study Type: Interventional
• Enrollment (Actual): 36
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • Michigan
    • Ann Arbor, Michigan, United States, 48109
      • University of Michigan

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 45 years (Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: Female

Description

Inclusion Criteria:

• Female
• Age = 18-45
• Premenopausal
• Body mass index ≥ 30 kg/m2
• Waist circumference ≥ 100 cm

Exclusion Criteria:

• Evidence of metabolic or cardiovascular disease
• Pregnancy
• Allergies to soybeans or eggs
• Hyperlipidemia (fasting plasma triglyceride concentration > 125 mg/dl)
• Hematocrit < 34%

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Weight loss - diet only	Behavioral: Weight loss - diet only; Subjects adhere to a reduced calorie diet until they lose exactly 12% of their initial body weight. After they achieve this weight loss goal, they are placed on a weight-maintaining diet for 3-4 weeks before follow-up experiments are performed. Subjects meet weekly with a research dietitian throughout their weigh-loss and weight maintenance program.
Experimental: Weight loss plus exercise	Behavioral: Weight loss plus exercise; Subjects adhere to a reduced calorie diet and perform 4 session of endurance exercise training per week until they lose exactly 12% of their initial body weight. Exercise training consists of stationary bicycle exercise. the exercise duration and intensity ramp up over the first few weeks of training until subjects exercise 45 min per session at an intensity of 85% of their maximal heart rate. 3 of the 4 exercise session each week are supervised by an Exercise physiologist. After they achieve the 12% weight loss goal, they are placed on a weight-maintaining diet for 3-4 weeks before follow-up experiments are performed. Subjects meet weekly with a research dietitian throughout their weigh-loss and weight maintenance program.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Insulin sensitivity	before and after 12% weight loss (3-6 months)

Secondary Outcome Measures

Outcome Measure	Time Frame
Rate of fatty acid mobilization in plasma	Before and after 12% weight loss (3-6 months)
Abundance and activity of Pro-inflammatory factors in skeletal muscle	Before and after 12% weight loss (3-6 months)
whole body and skeletal muscle oxidative capacity	Before and after 12% weight loss (3-6 months)

Collaborators and Investigators

• Sponsor: University of Michigan
• Collaborators: National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK); American Diabetes Association
• Investigators: Principal Investigator: Jeffrey Horowitz, PhD, University of Michigan

Publications and helpful links

General Publications

• Schenk S, Horowitz JF. Coimmunoprecipitation of FAT/CD36 and CPT I in skeletal muscle increases proportionally with fat oxidation after endurance exercise training. Am J Physiol Endocrinol Metab. 2006 Aug;291(2):E254-60. doi: 10.1152/ajpendo.00051.2006. Epub 2006 May 2.

Study record dates

Study Major Dates

• Study Start (Actual): June 1, 2003
• Primary Completion (Actual): January 1, 2007
• Study Completion (Actual): January 1, 2007

Study Registration Dates

• First Submitted: November 20, 2008
• First Submitted That Met QC Criteria: November 20, 2008
• First Posted (Estimate): November 21, 2008

Study Record Updates

• Last Update Posted (Actual): October 16, 2017
• Last Update Submitted That Met QC Criteria: October 12, 2017
• Last Verified: October 1, 2017

More Information

Terms related to this study

• Keywords: inflammation; Insulin sensitivity; fat metabolism
• Additional Relevant MeSH Terms: Glucose Metabolism Disorders; Metabolic Diseases; Immune System Diseases; Hyperinsulinism; Hypersensitivity; Insulin Resistance
• Other Study ID Numbers: ADA - 1-03-JF-10 (completed); ADA grant# 1-03-JF-10 (Other Grant/Funding Number: American Diabetes Association)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No