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Muscle triglyceride and insulin resistance
David E Kelley1, Bret H Goodpaster, Len Storlien
1Division of Endocrinology and Metabolism, Department of Medicine, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania 15213, USA. Kelley@msx.dept-med.pitt.edu
Annual Review of Nutrition
|June 11, 2002
Summary
Skeletal muscle triglyceride accumulation contributes to insulin resistance in obesity and type 2 diabetes. This inflexibility in fuel use impairs metabolic health.
Area of Science:
- Metabolic Physiology
- Endocrinology
- Molecular Biology
Background:
- Skeletal muscle is a primary site for energy storage, holding glycogen and intramyocellular triglycerides (imTG).
- Insulin resistance (IR) in obesity and type 2 diabetes mellitus (DM) is multifactorial, with skeletal muscle lipid content implicated.
- Metabolically healthy muscle efficiently switches between lipid and carbohydrate fuel utilization.
Purpose of the Study:
- To review the role of skeletal muscle triglyceride content in the pathogenesis of insulin resistance.
- To examine how altered fuel partitioning contributes to imTG accumulation.
- To discuss the inflexibility in fuel selection observed in skeletal muscle in obesity and type 2 DM.
Main Methods:
- Literature review of recent findings on skeletal muscle metabolism.
- Analysis of studies investigating lipid metabolism and fuel partitioning in skeletal muscle.
- Synthesis of evidence linking imTG accumulation to insulin resistance.
Main Results:
- Obesity and type 2 DM are associated with increased lipid content within and around skeletal muscle fibers.
- Altered fuel partitioning, favoring fat storage over oxidation, leads to imTG accumulation.
- Skeletal muscle in individuals with obesity and type 2 DM exhibits inflexibility in transitioning between lipid and carbohydrate fuels.
Conclusions:
- Accumulation of intramyocellular triglycerides in skeletal muscle is a key factor in the pathogenesis of insulin resistance.
- Inflexibility in fuel selection by skeletal muscle is linked to imTG accumulation and contributes significantly to IR.
- Understanding these mechanisms is crucial for developing targeted therapies for obesity and type 2 diabetes.
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