Excess Fat Causes “Epinephrine Resistance”
A trained bodybuilder's adipose tissue is much different than a sedentary person's adipose tissue. A trained individual in bodybuilding has increased fat-burning capacity compared to a sedentary person. Both basal and catecholamine-stimulated fat-burning capacities are higher in fat cells from trained individuals. An increase in fat mass results in an increase in insulin resistance and a reduced sensitivity to catecholamines. For example, young children who are overweight compared to lean children have a decreased triglyceride rate (approximately 30 percent) and are resistant to the actions of epinephrine.22
Obese patients tend to have elevated levels of circulating epinephrine, but are “epinephrine resistant,” much like obese people are “insulin resistant.” The reason for this could be that many obese patients are insulin resistant with high circulating insulin levels. Insulin causes a downregulation of the ? receptors (stimulate fat loss) on adipose tissue, which could lead to the epinephrine-resistant effects.23 Performing resistance exercise can increase insulin sensitivity and catecholamine sensitivity of adipose tissue, causing enhanced fat utilization.
In one experiment, 12 obese men performed three months of dynamic strength training. There was a significant reduction in fat mass with the strength training. Researchers took adipose tissue biopsies before and at the end of the study. In obese subjects, dynamic strength training improved whole-body and adipose tissue insulin sensitivity. The increased insulin sensitivity in adipose tissue also caused increased catecholamine sensitivity to epinephrine. It also increased lipolysis actions of catecholamines in fat cells.

Insulin Inhibits HSL Activity
As mentioned previously, insulin inhibits HSL activity. It should be no surprise that patients with type 2 diabetes mellitus (which results in elevated insulin levels) have decreased adipose tissue HSL mRNA and activity.12 In the December issue of MD, Dr. Dan Gwartney discussed the role of interleukin-6 (IL-6) and its ability to enhance fat oxidation. IL-6 is secreted by adipose and exerts lipolytic effects in adipocytes.13 Injections of recombinant human IL-6 infusion increase adipose tissue lipolysis in healthy humans, resulting in increased plasma fatty acid mobilization after prolonged (greater than two hours) infusion.14 Furthermore, acute rh IL-6 administration to patients with type II diabetes was found to increases HSL gene expression in adipose tissue.12 It may be that IL-6 exerts its effects on fat mobilization by increasing HSL activity, but further research is needed. So now that we’ve discussed the mechanisms of how HSL is reduced, let’s examine how to increase HSL and kick-start fat loss.

Epinephrine Increases Fat Metabolism
The physiological role of the sympathetic nervous system (SNS) is a major target of study for modulation of bodyweight and composition. The principle players in the SNS are hormones called catecholamines and the adrenergic receptors (adrenoceptors) upon which they act. Aside from insulin, catecholamines are the primary regulators of fat breakdown in cells by way of stimulation of adrenoceptors on the fat cell membrane. The activation of the sympathetic nervous system is involved in diet-induced thermogenesis, exercise and thermogenic supplements.
It’s also been reported that a reduced sympathetic nervous system may be a factor in future weight gain. In humans, catecholamines are potent activators of fat lipolysis, the breakdown of triglycerides from adipose tissue into glycerol and free fatty acids. Triglycerides are the stored form of fat used in energy metabolism. Fat cells are located in subcutaneous adipose tissue (under the skin), in the abdominal cavity surrounding organs (visceral fat) and between the cells of muscle and other tissues (intracellular lipids). Catecholamines (epinephrine and norepinephrine) are powerful stimulators of triglycerides from adipose tissue and exert their effect by binding to ?-adrenergic receptors (?1, ?2 and ?3 receptors), stimulating fat oxidation. Additionally, catecholamines prevent fat cell formation by blocking the actions of ?2 adrenoreceptors on white adipose cells.21 As stimulation of the ?-adrenoceptors can be thought of as the “on” switch for lipolysis, the ?2 adrenoreceptors can be considered the “off” switch.