Turning on the Metabolic Switches for Fat Burning
In human subcutaneous adipose tissue, adrenaline has a higher affinity for ?2 receptors than for ?-adrenergic receptors, suggesting the existence of a role for the ?2-adrenergic pathway in the control of fat lipolysis in humans.29 ?-adrenergic receptors modulate lipolysis during physical exercise and strong, sympathetic nervous system activation while ?2 receptors appear to be involved in the modulation of lipolysis at rest.32 Human fat cells contain three types of ?-adrenergic receptors (?1, ?2 and ?3 receptors), but ?1and ?2 are the most active in adipose tissue. Some studies suggest that obesity is attributed to an increase in ?2 receptors in adipose tissue. ?2 receptors could be an important component of the regulation of lipolysis in human fat cells; they’re mainly recruited at rest, under weak SNS activation or when specific activation of epinephrine release occurs. As mentioned previously, epinephrine blocks ?2 receptors on fat, which should prevent fat storage; however, for some reason obese people may have defects in this pathway. For example, using microdialysis (sticking probes directly into adipose tissue), exercise-induced fat mobilization was investigated in subcutaneous adipose tissue in obese subjects and compared with lean ones, and the effect of ?2 receptors blocker. The epinephrine and norepinephrine responses to exercise weren’t different in either group.

Interestingly, the changes in fat utilization from adipose tissue were greater in the lean group compared to the obese group during exercise (sixfold lower in obese men). In response to the ?2 receptors blocker, lean subjects didn’t have any change in lipolysis. However, lipolysis was strongly enhanced in the obese subjects and reached the concentrations found in lean subjects. These findings demonstrate that using an ?2 receptors blocker during exercise may enhance sympathetic nervous system activation and enhance lipolysis during exercise in obese men.30 So based on these findings, taking an ?2 receptors antagonist (yohimbine) can enhance fat utilization at rest, while taking a ?-receptor agonist before exercise can increase fat utilization during exercise.
The ideal fat-burning combination is one that increased ?-adrenergic activity and decreases ?2 adrenoreceptors activation. The major drugs that contribute to fat loss involve several major pathways via: 1) agents that increase cAMP levels through adenylate cyclase (?-agonists, caffeine, glucagon, forskolin), 2) suppression of adenosine effects in fat cell incubations (caffeine); and 3) the blocking action of ?2 adrenoreceptors (yohimbine).

Muscle Contractions Increases HSL Activity
Fat oxidation increases during exercise. The magnitude of the increase and the relative contribution it makes to energy transfer depends on the complex interaction of a number of factors that aren’t entirely understood at this time. The intensity of exercise, the duration of exercise, the state of training and nutritional status are important factors influencing fat oxidation.
With intense exercise, epinephrine, norepinephrine and insulin levels are suppressed. Raising exercise intensity from 25 percent of your maximal aerobic capacity to 65 percent of your maximum aerobic capacity appears to be related to increasing levels of epinephrine concentration with a similar rise in HSL activity.1 It’s been reported that muscle contractions by themselves can increase HSL activity in muscle. It’s also been reported that electrically induced contractions can increase HSL activity without increased circulating levels of catecholamines. In one experiment, HSL activity in muscle increased significantly within the first minute of contractions, and this increase was maintained for 5 minutes of stimulation.24
During exercise, consuming carbohydrates may not be the way to go if you’re trying to get ripped. Researchers have found that carbohydrate ingestion during exercise increases plasma insulin and decreases plasma epinephrine concentrations induced by carbohydrate ingestion, which also led to suppression in HSL activity.26 The results of the study suggest that increases in plasma insulin and suppression of catecholamines will suppress HSL activity.

High-intensity Exercises Drives Catecholamines and EPOC
Epinephrine and norepinephrine are potent stimulators of energy metabolism during exercise through ?-receptor activation in fat and muscle. During dynamic exercise, catecholamines increase linearly with exercise duration and intensity.16,17 Catecholamines have also been reported to be one of the many regulators of metabolism after exercise (called exercise post-oxygen consumption or EPOC). EPOC consists of two components: a fast component that lasts less than an hour and a slow component that lasts several hours. The presumed metabolic components responsible for the fast component of EPOC are replenishment of O2 stores in blood and muscle, resynthesis of ATP, Creatine, lactate removal and increased ventilation circulation.19 Mechanisms of the slow EPOC component are more complex. Some of the components responsible for the slow phase include elevated temperature, catecholamines and replenishment of muscle glycogen.
Increasing both GH and catecholamines by increasing exercise intensity may provide a dual effect on fat loss by different mechanisms. Weltman et al.8 reported a dose-dependent response between lactate and GH levels to low- and high-intensity running protocols. In that study, five treadmill-running intensities were studied at various percentages of the subjects’ lactate threshold (LT; 0.25 LT, 0.75 LT, LT, 1.25 LT and 1.75 LT). The results of the study concluded that the degree of fat utilization post-exercise was directly related to the increases in GH and epinephrine secretion during exercise.36 Additionally, the degree of fat utilization during the recovery period was related to the exercise intensity level. High-intensity resistance exercise leads to a rapid increase in catecholamines, which may enhance EPOC. In one study, researchers reported that when subjects were given a drug that suppresses catecholamines during exercise, there was no increase in metabolism or EPOC after exercise.18 Burleson et al.25 compared EPOC in response to resistance exercise and treadmill exercise performed at the same caloric energy expenditure. Results of the study concluded that resistance exercise led to a significantly higher EPOC than the treadmill due to greater increases in heart rate, lactate and fat utilization during resistance exercise. EPOC was approximately 50 percent higher than the treadmill protocol. Another possible mechanism for enhanced fat loss with epinephrine is increased blood flow to adipose tissue. In last month's research update column, it was reported that an increase in blood flow during exercise may enhance fat mobilization. Simonsen et al. reported that blood flow and 02 uptake increased in skeletal muscle and adipose tissue after infusions of adrenaline, but the largest contributor of thermogenesis was from adrenaline’s action on skeletal muscle.20

Crank Up those Catecholamines for Fat Loss
It’s been known for many years that white adipose tissue is innervated (connected by nerves) by the sympathetic nervous system. Taking drugs that increase catecholamines stimulate the sympathetic nervous system, which is why, in addition to feeling a little jittery, there’s increased fat mobilization occurring. Every bodybuilder knows that getting the glutes ripped is much harder than getting a six-pack. The reason is that abdominal adipose tissue is rich in ? receptors and is more responsive to ? agonists (catecholamines, clenebuterol) than adipose tissue from the glutes.7 The stimulation of the sympathetic nervous system leads to decreases in fat cell number.
If you cut the nerves to adipose tissue or block the actions of catecholamines, there’s an increase in fat cell size.6 When you gain fat mass, adipose tissue fills with lipids and gets to a critical size, then precursor cells are stimulated to make new adipose tissue. In one study, within a week of reduced sympathetic stimulation there was an increased number of preadipocytes and also an increase in the number of mature adipocytes. Interesting, the reduction of sympathetic nervous activity didn’t affect any metabolic parameter such as glucose metabolism, LPL (fat storage enzyme) or HSL activity. What this means is that you have to keep your sympathetic nervous system fired up to prevent future weight gain and lose body fat.