The Rate-limiting Enzyme for Fat Metabolism
How would you like to eat as much fat as you want and never gain weight? Researchers have developed a mouse model where they genetically altered the activity of a key fat-mobilizing hormone called hormone-sensitive lipase (HSL). These mice can eat higher calories and fat and are resistant to weight gain, have a higher body temperature and increased resting energy expenditure compared to normal mice. Even more impressive, HSL-genetically altered mice have white adipose tissue that’s 70 percent lower compared to normal mice.8 HSL is the rate-limiting step for the liberation of fats from adipose tissue and muscle into circulation and ultimately for use as a fuel source during exercise. HSL isn’t only regulated by muscle contractions,3 but also by epinephrine as well.4,5

When HSL is increased in muscle, fatty acids are liberated from intramuscular lipids where they’re utilized by muscle fibers as an energy source. With regard to muscle contraction, HSL activity appears to be increased by the frequency and duration of exercise as a result of changes in muscle glycogen. Low glycogen stores induced by a low-carbohydrate diet increase HSL activity in muscle.27 A recent 2006 study in the Journal of Lipid Research reported that stimulation with both muscle contractions and epinephrine can result in significant decreases in reduction in the number as well as the size of lipid droplets.31 Good old caffeine has also been shown to cause a moderate increase (approximately 17 percent) in muscle HSL (TG) activity.34 With muscle contractions able to stimulate HSL activity in muscle, it would probably make sense to use high repetition and high volume during precompetition for maximal stimulation of HSL activity during exercise.

The Male Pregnant Gut Syndrome: A Deficiency in HSL
Catecholamines are the main stimulatory hormones accelerating fat burning. It’s well established that catecholamine action in adipose tissue is reduced in obese people. This could be due to three mechanisms that alter adipose tissue function with obesity: 1) increased expression of ?2 receptors, which promote fat storage; 2) decreased expression of ?2-adrenoreceptors, which stimulate fat utilization; and 3) decreased expression of HSL activity.
Ever notice that some men have normal lower body phenotypes, but also have the pregnant gut syndrome? It’s interesting that when women become pregnant there’s an increase in HSL activity in adipose tissue to supply the baby with a rich source of energy from adipose tissue. In contrast to pregnant females, a reduction in adipose tissue HSL is part of the pregnant gut syndrome in men.

It’s been observed that in obese individuals there’s a decreased ability of catecholamines to induce fat mobilization in subcutaneous adipose tissue, partly explained by the decreased activity of HSL activity in obese subjects.9 It's also interesting to note that in obese abdominal fat cells, larger fat cells secrete more HSL than smaller adipose cells.11 Scientists have hypothesized that the reason for this is the body’s fat-burning capacity is stimulated as an adaptive mechanism to limit further increases in fat cell size. It's your body's way of saying, "So fat-ass, since you won't stop eating I’m going to increase your fat-burning enzymes so you won't get any fatter!!" Some males are born with a defect in the HSL gene in adipose tissue, which makes them obese. Researchers took adipose tissue samples from men with the defective HSL genetics and found that when they exposed adipose cells to several different drugs (norepinephrine, forskolin, cAMP agents, etc.) to stimulate fat mobilization, there was a 50 percent reduction in the activity of adipose cells to the agents.10 This suggests that a reduction in adipose tissue HSL activity may be a mechanism whereby people become obese. A decrease in HSL activity may also contribute to age-related increases in fat mass as well. In elderly subjects, there’s a decrease in catecholamine-stimulated lipolysis that’s due to a decrease in HSL activity, in addition to an increase in insulin resistance.35