November 16, 2009

Muscle Energy Metabolism

The Department of Health and Human Services 2008 Physical Activity Guidelines recommends the following physical activity guidelines:
Children 6-17 should engage in 1 hour of moderate physical activity on most days of the week, and should perform bone strengthening or muscle strengthening exercises at least 3 days out of the week.
Adults 18-64 years old should engage in 2 hours and 30 minutes of moderate activity per week where at least 2 days out of the week activities are muscle strengthening and conditioning. OR adults should get 75 minutes of vigorous activity during the week where at least 2 days out of the week activities are muscle strengthening and conditioning.
Adults older than 65 years old should follow the recommendations (within their physical limits) for adults, and healthy pregnant women can follow the same for adults.

Why does it all matter? Exercise increases the oxidative capacity of muscle and inactivity causes reductions in the oxidative capacity of muscle. This oxidative capacity allows muscles to generate enormous amounts of kinetic energy. Skeletal muscle contributes to lipid and glucose homeostasis, and imbalances in this homeostasis can contribute to dysmetabolic disorders including insulin resistance, type 2 diabetes, dyslipidemias (increased LDL and VLDL's with reductions in HDL, and overall high trigylcerides). Exercise promotes weight stabilization, weight loss, and weight maintenance, blood glucose control, and calorie imbalance. In addition, exercise increases the capillary density promotiong the oxygen carrying capacity of muscles and can contribute to increasing the VO2 max. Exercises causes muscle fiber hypertrophy, or increases in muscle mass size. Oxidative capacity is increased by increasing the mitochondrial density, increasing TCA cycle enzymes, and increasing beta-oxidation enzymes. Together, these functions make exercise a necessity in maintaining and achieving health.

1. Why does skeletal muscle have a major impact on energy balance and body weight?
Ultimately, muscles perform mechanical energy, and their ability to do this relies on several biochemical processes and physiological functions. Muscles are the major sites of fatty acid oxidation and muscles take up glucose from the body to sustain the energy needed for glycogen synthesis, amino acid repair and muscle triacylglycerol synthesis. When you exercise you burn energy either as glucose or fatty acid oxidation (the substrate depends on the length, duration and type of conditioning) which leads to a caloric imbalance which can be related to body weight. Too little activity results in an imbalance of calories because calories in does not equal calories out. Weight is maintained (through many other mechanisms) but calories in = calories out.

2. How does skeletal muscle contribute to glucose and lipid homeostasis?
Muscle is dynamic tissue in that it performs a series of metabolic processes that has a wide range of effects. Essentially in healthy exercised muscles, glucose and lipids are readily and rapidly taken up into muscle. In unhealthy non-exercised muscles glucose and lipids interfere with cell signaling because so much is getting stored within the muscle, and more wants to get into the muscle. This imbalance can cause insulin resistance, dyslipidemia, cardiovascular disease, and other dysmetabolic states.

Glucose enters muscle cells via GLUT 4 receptors. These receptors translocate or move to the surface of the muscle cell and allow entry of glucose into the cell. GLUT 4 receptors mediate the entry of glucose in the cells for physiological function of the muscle cell. This contributes to glucose homeostasis because glucose is readily cleared from circulation and put into "storage." Problems occur when this balance is not achieved.

Skeletal muscle is a major site of fatty acid oxidation so healthy active muscles account for a large clearance of serum lipids including fatty acids, chylomicron, triaclglycerol, and VLDL's. After activity the muscle takes up lipids and uses the energy for glycogen resynthesis, muscle TAG synthesis and protein synthesis. This is caused by an increase in lipoprotein lipase activity. The way muscle contributes to lipid homeostasis is by burning energy, taking up lipids for fuel and refueling essential muscle functions (growth, repair). It also decreases VLDL and LDL, but raises HDL. These major functions contribute to lipid homeostasis.

Too much lipid or fat stored within the muscle as a direct effect of inactivity and calorie imbalance may result in insulin resistance and be on the causal pathway to developing diabetes. Lipids secrete adipokines, which are fat proteins that signal the general health status of the fat cell. Some adipokines such as TNFa are inflammatory markers and the presence of these in tissues where they should not normally be may contribute to abnormal cell signaling. The mechanism of action here is that the GLUT 4 receptor is not able to translocate to the cell surface, because of a defect in the insulin signaling pathway. Peripheral insulin resistance can be linked to skeletal muscle. Activity and exercise can reverse or improve insulin resistance by increasing or returning the oxidative capacity functions.

Muscles play an integral role in lipid and glucose homeostasis and chronic disease development. Exercising promotes the oxidative capacity of muscle tissue. This is directly linked to prevention of many chronic diseases including type 2 diabetes, metabolic syndrome, and cardiovascular diseases. In addition, exercise promotes weight maintenance and weight loss, improves circulation, promotes healthy blood pressure, strengthens the blood vasculature, promotes bone and skeletal health, and may prevent cancers of the breast and colon.

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