Fatty Acid Metabolism and Insulin Sensitivity: the Role of Endurance Exercise
Condition: Insulin Resistance and Type 2 Diabetes
MeSH terms: Insulin Resistance; Hypersensitivity
Study type: Interventional

Summary: 
      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.
    

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.
    

Intervention name(s): Weight loss - diet only; Weight loss plus exercise
Intervention type(s): Behavioral; Behavioral
Intervention description(s): 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.; 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.
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Primary purpose: Basic Science
Keywords: Insulin sensitivity; fat metabolism; inflammation