|The Physiology of Fat Loss
Mike Deyhle, Christine Mermier, Ph.D. and Len Kravitz, Ph.D.
Fat serves many important functions in the human body. For example, fat provides a key role for the structure and flexibility of cell membranes and also helps to regulate substance movement through the cell membranes. Special types of fat (known as eicosanoids) can do specialized hormone signaling, exerting intricate control over many bodily systems, mostly in inflammation or for immune function. Perhaps the most well known function of fat is as an energy reserve. Fat serves the role of an efficient energy store because it can hold a lot of energy per gram. In fact, fat yields more than two times the Calories per gram than that of carbohydrate (9 Calories/gram for fat versus 4 Calories/gram for carbohydrate). It has been estimated that lean adult men store about 131,000 Calories in fat (Horowitz & Klein, 2000). That is enough energy to sustain life for the average person for approximately 65 days. Excessive fat storage can be unhealthy and/or unwanted. Reducing body fat, whether for health, sports performance or body image reasons, is often a client's goal when working with a personal trainer, and is the focus of this article.
The Journey of a Fatty Acid to Muscle
Fat is primarily stored in designated fat storage cells called adipocytes. For the most part, adipocytes are located just under the skin throughout the body as well as in regions surrounding vital organs (for protection) called visceral fat. Most of the fat inside the adipocytes is in the form of a triacylglycerol (TAG or triglyceride). TAGs are composed of a backbone (glycerol) with 3 fatty acid tails.
Depending on energy supply and demand, adipocytes can take up and store fat from the blood or release fat back to the blood. After eating, when energy supply is high, the hormone insulin keeps the fatty acids inside the adipocyte (Duncan et al., 2007). After a few hours of fasting, or especially during exercise, insulin levels tend to drop while other hormones such as epinephrine (otherwise called adrenaline) increase. When epinephrine binds to the adipocyte it causes lipolysis of the TAG stores in the adipocyte (Duncan et al., 2007). Lipolysis is the separation of the fatty acids from the glycerol backbone. After lipolysis, the fatty acids and glycerol can leave the adipocyte and enter the blood.
Fatty Acids In the Blood
The blood is an aqueous (water based) environment. Because fat is not water-soluble (i.e., it does not dissolve or mix well in water), a carrier protein is required to keep it evenly suspended in the blood. The primary protein carrier for fat in the blood is albumin (Holloway et. al. 2008). One albumin protein can carry multiple fatty acids through the blood to the muscle cell (Horowitz and Klein, 2000). In the very small blood vessels (capillaries) surrounding the muscle, fatty acids can be removed from albumin and taken into the muscle (Holloway et al., 2008).
Fatty Acids From the Blood into the Muscle
In order for fatty acids to get from the blood into the muscle they must cross two barriers. The first is the cell lining that makes up the capillary (called the endothelium) and the second is the muscle cell membrane (known as the sarcolemma). Fatty acid movement across these barriers was once thought to be extremely rapid and unregulated (Holloway et al., 2008). More recent research shows that this process is not nearly as rapid as once thought and that it requires special binding proteins present at the endothelium and sarcolemma to take in fatty acids (Holloway et al. 2008). Two proteins that are important for fatty acid transport into the muscle cell are FAT/CD36 and FABPpm.
The Two Fates of Fat Inside the Muscle
Once inside the muscle, a molecule called Coenzyme A (CoA) is added to the fatty acid (Holloway et al., 2008). CoA is a transport protein which maintains the inward flow of fatty acids entering into the muscle and prepares the fatty acid for two fates: 1) oxidation (a process in which electrons are removed from a molecule) to produce energy or, 2) storage within the muscle (Holloway et al. 2008, Shaw, Clark & Wagenmakers 2010). The majority (80%) of fatty acids entering the muscle during exercise are oxidized for energy while most fatty acids entering the muscle after a meal are repackaged into TAGs and stored in the muscle in a lipid droplet (Shaw, Clark & Wagenmakers, 2010). Fat that is stored inside the muscle is called intramyocellular triacylglycerol (IMTAG or intramuscular fat). The amount of IMTAG in slow twitch muscles (the slow oxidative fibers) is two to three times greater than the IMTAG stored in fast twitch muscles fibers (Shaw, Clark and Wagenmakers). Shaw and colleagues continue that even though this IMTAG content makes up only a fraction (<1% to 2%) of the total fat stores within the body, it is of great interest to exercise physiologists. This is because it is a metabolically active fatty acid substrate especially used during periods of increased energy expenditure, such as endurance exercise.
Fatty Acids Burned for Energy
Fatty acids burned for energy (oxidized) in the muscle can either come directly from the blood or from the IMTAG stores. In order for fatty acids to be oxidized, they must be transported into the cell's mitochondria. The mitochondrion is an organelle that functions like a cellular power plant. The mitochondrion processes fatty acids (and other fuels) to create a readily usable energy currency (ATP) to meet the energy needs of the muscle cell. Most fatty acids are transported into the mitochondria using a shuttle system called the carnitine shuttle (Holloway et al. 2008). The carnitine shuttle works by using two enzymes and carnitine (an amino acid-like molecule) to bring the fatty acids into the mitochondria. One of these enzymes is called carnitine palmitoyl transferase I (CPTI). CPT1 may work with one of the same proteins (FAT/CD36) used to bring fatty acids into the muscle cell from the blood (Holloway et al. 2008). Once inside the mitochondria, fatty acids are broken down through several enzymatic pathways including beta-oxidation, tricarboxylic acid cycle (TCA), and the electron transport chain to produce ATP.
Focus Paragraph: An Overview of Fat Metabolism in the Mitochondrion
Fatty acids are transported into the muscle where they are either stored (as IMTAG) or transported into the mitochondrion, which can be referred to as the fat-burning furnace in a person's body cells (as this is the only place TAG are completely broken down). As the chemical bonds in TAG molecules are broken up in metabolism they begin to lose electrons (a process called oxidation) and are picked up (a process called reduction) by electron transporters (NADH+H+ and FADH2). The electron transporters take the electrons to the electron transport chain for further oxidation, which leads to a liberation of energy that is used to produce adenosine triphosphate (ATP). Unused energy becomes heat energy to sustain the body's core temperature. This ATP synthesizing process depends upon a steady supply of oxygen, which is why this process is aptly nicknamed aerobic metabolism or aerobic respiration.
Adapted from Achten, J., and Jeukendrup, A.E. 2012.
Fatty Aid Oxidation During a Single Bout of Exercise
At the start of exercise blood flow increases to adipose tissue and muscle (Horowitz and Klein, 2000). This allows for increased fatty acid release from adipose tissue and fatty acid delivery to the muscle. Exercise intensity has a great impact on fat oxidation. Maximal fat oxidation occurs at low to moderate intensity (between 25% and 60% of maximal oxygen consumption (VO2max) (Horowitz & Klein 2000). At lower exercise intensities, most of the fatty acids used during exercise come from the blood (Horowitz & Klein 2000). As exercise increases to moderate intensity (around 60% of VO2max) the majority of fatty acids oxidized appear to come from IMTAG (Horowitz and Klein, 2000). At higher exercise intensities (>70 % VO2max), total fat oxidation is reduced to levels lower than that of moderate intensity (Horowitz and Klein, 2000). This reduced rate of fatty acid oxidation is coupled with an increase in carbohydrate breakdown to meet the energy demands of the exercise (Horowitz & Klein, 2000).
This counterintuitive drop in fat utilization during high intensity exercise is caused by several factors. One factor is related to blood flow to adipose tissue and thus reduced fatty acid supply to the muscle. At high exercise intensity, blood flow is shunted (or directed) away from adipose tissue so that fatty acids released from adipose tissue become trapped in the adipose capillary beds, and are not carried to the muscle to be used (Horowitz and Klein, 2000). Another reason for reduced fat usage at high exercise intensities is related to the enzyme CPT1. CPT1 is important in the carnitine shuttle that moves fatty acids into the mitochondria for oxidation. The activity of CPT1 can be reduced under conditions of high intensity exercise. Two mechanisms are thought to reduce CPT1 activity during intense exercise. As stated above, with increasing exercise intensity fatty acid oxidation drops while carbohydrate oxidation increases. The increased usage of carbohydrate leads to increased levels of a molecule called malonyl CoA inside the cell (Horowitz and Klein, 2000). Malonyl CoA can bind to and inhibit the activity of CPT1 (Achten and Jeukendrup, 2012).
Another way intense exercise may reduce CPT1 activity is by changes in cellular pH. The cellular pH is the measure of the acidity in the cell's cytoplasm (fluid) in terms of the activity of hydrogen ions. As exercise intensity increases the muscle becomes more acidic. Increased acidity (which means the pH is lowering) can also inhibit CPT1 (Achten and Jeukendrup, 2012). The reason for the increased acidity during high intensity exercise is not because of lactic acid formation as once thought. Instead, acidosis increases because the muscle is using more ATP at the contracting muscle fibers (just outside of the mitochondria), and the splitting of ATP releases many hydrogen ions into the cellular fluid (sarcoplasm) leading to the acidosis in the cell (Robergs, Ghiasvand and Parker, 2004).
Too much emphasis is often placed on percent of fatty acid contribution of Calories burned during a single bout of exercise. Recovery from a bout of exercise as well as training adaptations to repeated bouts are important to consider when working with clients with fat loss goals.
Focus Paragraph. The Splitting of Adenosine Triphosphate (ATP)
ATP is split by water (called hydrolysis) with the aid of the ATPase enzyme. During intense exercise there is a high level of hydrolysis of ATP by the muscles fibers. Each ATP molecule that is split releases a hydrogen ion, which is the cause of acidosis in the cell (Robergs, Ghiasvand and Parker, 2004). This acidosis can slow the carnitine shuttle that moves fatty acids into the mitochondria for oxidation.
Energy/Fat Used During Recovery
After exercise an individual burns more energy, which is primarily used for muscle cell recovery and glycogen replacement with the muscle. This elevated metabolic rate is termed excess post exercise oxygen consumption (EPOC). EPOC appears to be greatest when exercise intensity is high (Sedlock, Fissinger and Melby, 1989). For example, EPOC is higher after high intensity interval training (HIIT) compared to exercise for a longer duration at lower intensity (Zuhl and Kravitz, 2012). EPOC is also notably observed after resistance training (Ormsbee et al. 2009), because it disturbs the working muscle cells' homeostasis to a great degree resulting in a larger energy requirement after exercise to restore the contracting muscle cells to pre-exercise levels. EPOC is particularly elevated for a longer period of time after eccentric exercise due to additional cellular repair and protein synthesis needs of the muscle cells (Hackney, Engels, and Gretebeck, 2008). Many studies also show that during the period of EPOC, fat oxidation rates are increased (Achten and Jeukendrup, 2012, Jamurtas et al. 2004, and Ormsbee et al., 2009). Comparatively, fatty acid use during high intensity bouts of exercise such as HIIT and resistance training may be lower as compared to moderate intensity endurance training; however, high intensity exercise and weight training may make up for this deficit with the increased fatty acid oxidation through EPOC.
Focus Paragraph. Comparison of Effect of Light Exercise versus Heavy Exercise on EPOC
Some key factors that contribute to the elevated post-exercise oxygen consumption during high intensity exercise include the replenishment of creatine phosphate, the metabolism of lactate, temperature recovery, heart rate recovery, ventilation recovery, and hormones recovery (Sedlock, Fissinger and Melby, 1989).
Adaptations to Exercise that Improve Fat Usage
Trained people are able to use more fat at both the same absolute (speed or power output) and relative (% of VO2 Max) exercise intensity than untrained people (Achten and Jeukendrup, 2012). Interestingly, lipolysis (breakdown of fats to release fatty acids) and fat release from adipocytes is not different between untrained and trained people (Horowitz and Klein, 2000). This suggests that the improved ability to burn fat in trained people is attributed to differences in the muscle's ability to take up and use fatty acids and not the adipocyte's ability to release fatty acids. The adaptations that enhance fat usage in trained muscle can be divided into two categories: 1) those that improve fatty acid availability to the muscle and mitochondria and 2) those that improve the ability to oxidize fatty acids.
Fatty acid availability
One way exercise can improve fatty acid availability is by increasing fatty acid transport into the muscle and mitochondria. As mentioned above, specific proteins mediate transport of fatty acids into the muscle and mitochondria. Exercise training has been shown to increase the amount of FAT/CD36 on the muscle membrane and mitochondrial membrane (Holloway et al. 2008) and has been shown to increase CPT1 on the mitochondrial membrane (Horowitz and Klein 2000). Together these proteins will improve fat transport into the muscle and mitochondria to be used for energy.
Exercise may also cause changes in the intramuscular lipid droplet (that contains IMTAGs). The intramuscular lipid droplet is mostly found in close proximity to the mitochondria (Shaw, Clark and Wagenmakers, 2010). Having IMTAGs close to the mitochondria makes sense for efficient IMTAG usage so that fatty acids released from the lipid droplet do not have to travel far to reach the mitochondria. Exercise training can further increase IMTAG availability to the mitochondria by causing the lipid droplet to conform more closely to the mitochondria. This increases surface area for more rapid fatty acid transport from the lipid droplet into the mitochondria (Shaw, Clark and Wagenmakers, 2010). Exercise training may also increase the total IMTAG stores (Shaw, Clark and Wagenmakers, 2010).
Another training adaptation that may improve fatty acid availability is increased number of small blood vessels within the muscle (Horowitz and Klein, 2000). Remember, fatty acids can enter the muscle through the very small blood vessels. Increasing the number of capillaries around the muscle will allow for increased fatty acid delivery into the muscle.
Fatty acid breakdown
IMTAGs are a readily available substrate for energy during exercise because they are already located in the muscle. Trained athletes have an increased ability to use IMTAG efficiently during exercise (Shaw, Clark and Wagenmakers, 2010). Athletes also tend to have larger IMTAG stores than lean sedentary individuals. Overweight and obese individuals, interestingly, also have high levels of IMTAG but are not able to use IMTAGs during exercise like athletic individuals can (Shaw, Clark and Wagenmakers, 2010).
So what causes the reduced ability to use IMTAGs in obese individuals? A logical guess would be that they have dysfunctional mitochondria that cannot use fatty acid properly. Research has shown however, that the mitochondria from muscles of obese individuals are not dysfunctional (Holloway et al. 2008). Instead, the number of mitochondria per unit of muscle (mitochondrial density) is reduced in an obese population (Holloway et al. 2008). Reduced mitochondrial density is a more likely explanation for reduced ability to use fat for energy in obese individuals. An important adaptation to exercise training is increased mitochondrial density (Horowitz and Klein 2000; Zuhl and Kravitz, 2012). Increasing mitochondrial density would improve the ability to use fat and benefit individuals with fat loss goals.
Endurance exercise training is an effective way to improve the body's fatty acid usage abilities by improving the availability of fatty acids to the muscle and mitochondria and by increasing fatty acid oxidation (Horowitz and Klein, 2000). HIIT training has also been shown to result in similar fat burning adaptations while requiring fewer workouts and less total time commitment (Zuhl and Kravitz, 2012)
Rather than trying to maximize fat oxidation in a single bout of exercise, it is recommended that the personal trainer design a workout program aimed at causing muscle adaptations described above to improve fatty acid oxidation ability. The exercise professional should include interval and endurance training programs as these have been shown to improve mitochondrial density and fat oxidation (Zuhl and Kravitz, 2012). In addition, regular progressively increasing programs of resistance training are encouraged as this training will enhance EPOC and post-workout fat oxidation. Also, the personal trainer should encourage the client to engage in low to moderate intensity exercise (such as walking and cycling) on off hard workout days in order to enhance caloric deficit and support muscle adaptions between training days.
High intensity interval training (HIT) with variable recovery (modified from Seiler and Hetlelid, 2005)
High intensity interval training uses exercise intensity that corresponds to the individual's VO2max. Seiler and Hetlelid (2005) exercised subjects at their highest running speeds for 4 minutes with 1, 2 or 4 minutes of recovery and repeated this interval 6 times. The trainer can do HIT with clients with many different modes of exercise, simply having the client maintain his/her maximal sustained exercise effort for the 4 minutes. The idea of a systematic variation of the recovery is a very novel approach to interval training and certainly warrants more research.
Have the client complete up to 6 sets of 4-minute bouts at a maximal sustained workout effort and vary each recovery period to be 1 min, 2 min or 4 minutes at a light intensity (client's self-selected intensity).
Sprint interval training (SIT) (Modified from Burgomaster et al. 2008)
Sprint interval training is repeated all-out (maximum effort) bouts of exercise. The maximal effort generated in SIT necessitates a small work to larger rest ratio. That is, SIT is often done with a 30-second all-out effort followed by a 4.5-minute rest period. The trainer can do SIT with clients using a variety of different modes of exercise including the stationary bike, elliptical cross-trainer and rowing machine. The resistance on the chosen mode of exercise should be relatively challenging during the work bout. During the sprint interval the trainer should verbally encourage the client to maintain maximal effort throughout the bout. During the recovery phase between bouts the client is encouraged to continue moving on the exercise machine at a very low self-selected light effort.
Have the client complete 3 to 4 bouts of 30-second all-out bouts bout with 4.5 minutes of active recovery between bouts.
This is a very challenging workout. Modifications may be required to match the individual's fitness level needs.
Resistance Training (RT) (modified form Melby et al. 1993)
This workout is a slight modification of others that have been shown to cause EPOC (Melby et al. 1993) and increased fat usage (Jamurtas et al. 1993) in time period after the exercise. This is total body weight lifting workout that uses 10 exercises. The exercises are arranged in 5 pairs so that each pair of exercise is completed before resting and moving on to the next pair. The whole circuit of exercise should be completed up to 6 times. The rest interval between pairs should be no longer than 2 minutes. The resistance used on each exercise should allow the client to lift 8 to 12 repetitions.
o Pair 1
o Bench press
o Bent over row
o Pair 2
o Split squat (Right leg forward)
o Split squat (Left leg forward)
o Pair 3
o Military press
o Pair 4
o Biceps curls
o Triceps extensions
o Pair 5
o Half squat
o Lateral raises
As with any workout, exercise modifications or substitutions may be necessary to fit individual's fitness needs and abilities.
Tabata-inspired interval training (modified form Tabata et al., 2006)
Tabata-style intervals use 20 seconds of high-intensity work followed by 10 seconds of rest, repeated up to eight times. Tabata-style training can use cardiovascular equipment such as the treadmill, rowing machine or stationary bike, or in calisthenics such as burpees, mountain climbers or body-weight squats. During the rest interval, keep the client moving to avoid blood pooling in the lower extremities. This will also help prevent the client from feeling queasy or faint.
Have the client perform complete three sets of Tabata intervals, resting 3 minutes between sets. Use burpees for the first set, the stationary bike for the second and the rowing machine for the third. Workout should last about 21 minutes.
This type of exercise has been shown to be effective at improving VO2max. Encourage the client maintain a challenging effort during this workout. The personal trainer should provide verbal encouragement to help the client do this.
Moderate intensity steady-state exercise (MIR)
Light-to-moderate exercise should be encouraged on days when the client is recovering from one of the more intense condition workouts provided here. This exercise should be restorative, allowing for the client's body to promote new muscle adaptations they have gaining from the more intense training.
Walking is a great way to implement this workout. Encourage the client to walk around their neighborhood or local park for 30 minutes to 1 hour. The walking pace should be that which the client can sustain a conversation.
Mike Deyhle, B.S, CSCS, is an Exercise Science masters student at the University of New Mexico, Albuquerque. He is interested in neural and skeletal muscular physiology especially with respect to skeletal muscular damage, metabolism, fatigue, and exercise training/detraining.
Christine Mermier, Ph.D. is an assistant professor and exercise physiology laboratory director in the exercise science Program at UNM. Her research interests include the effect of exercise in clinical patients, women, and aging populations, and high altitude physiology.
Len Kravitz, PhD, is the program coordinator of exercise science and a researcher at the University of New Mexico, Albuquerque, where he won the Outstanding Teacher of the Year award. He has received the prestigious Can-Fit-Pro Lifetime Achievement Award and American Council on Exercise Fitness Educator of the Year.
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