Trying to get ripped up for a competition or for personal goals can be an extremely difficult feat to accomplish. Everyone wants to have that ripped look where your skin is paper-thin and veins popping out everywhere but achieving that look takes an extreme amount of will-power, guts, and dedication in the gym.
Trying to get ripped up for a competition or for personal goals can be an extremely difficult feat to accomplish. Everyone wants to have that ripped look where your skin is paper-thin and veins popping out everywhere but achieving that look takes an extreme amount of will-power, guts, and dedication in the gym. Your body whom does not understand the mind of a bodybuilder thinks, "I starving, there is a drought, calories are insufficient, I am losing bodyfat…slow down all metabolic systems until bodyfat return to normal." Your own body tries to sabotage your competition goals of losing fat by slowing down your metabolism and breaking down lean muscle mass as an energy source. During a calorie-restricted diet the sympathetic nervous system is decreased, this decrease in sympathetic nerve activity results in a reduction in lower metabolic rate thus conserving reserves of nutrients, although this is not necessarily true for adipose tissue (1). During fasting or calorie restriction, adipose tissue readily releases stored energy. That is where thermogenic supplements come in handy because they increase sympathetic nervous system activity and restores sympathetic tone. One of the ways caffeine and ephedrine stimulates lipolysis is by increasing the release of the "fight-or flight" hormones called catecholamines. The major catecholamines are dopamine, norepinephrine, and epinephrine (also known as adrenaline). Maintaining or increasing lean body mass should be one of the most important strategies for any weight reduction program. By maintaining lean muscle, mass during dieting maintains the body's thermogenic response to food and basal metabolic rate.
Catecholamines' and Adipose Tissue Regulation
Stimulating fat metabolism is the result of mobilizing fat stores in which stored fat is mobilized by the hydrolysis of free fatty acids and glycerol. This is initiated by the rise in a variety of hormones such as norepinephrine, epinephrine, ACTH, and glucagon. The mechanisms of these lipolytic hormones are believed to be mediated by an increase in cAMP. Lipolytic hormones activate adenylate cyclase, resulting in increased synthesis of cAMP-dependent protein kinases and subsequent phosphyorylation and activation of hormone-sensitive lipase, resulting in the hydrolysis of stored triglycerides to glycerol and free fatty acids (2).
Hormone sensitive lipase is the rate-limiting enzyme in triglyceride breakdown and lipolysis.
Adenylate Cyclase is an enzyme that activates cAMP or Cyclic Adenosine Monophosphate in the cell. cAMP promotes breakdown of stored fats, regulates thermogenic responses to food, increases the body's basal metabolic rate, and increases the utilization of body-fat.
Catecholamines increase fat lipolysis and reduce adipogenesis or the creation of new fat (3). During calorie-restricted diets, normally there is a rise in free fatty acids and glycerol as fats are mobilized as an energy source. Catecholamines are so important to stimulating lipolysis that if a person is fasting and is administered a ß adrenergic blockade drug such as propranolol (i.e. a drug that blocks the sympathetic nervous system) the rise in serum fatty acids and glycerol is abolished (4). The use of GH is a great drug for stimulating lipolysis. Chronic exposure to GH increases the responses to catecholamines; the mechanism in unclear, but the hormones can increase the ß adrenergic receptor number and increase cAMP production (5). Interestingly, glucocorticoids such as cortisol also increase ß adrenergic receptor number, but decrease maximal adenylate cyclase activity and reduce cAMP production in fat cells reducing fat loss (6). On adipose tissue, there are several types of receptors that are of interest to stimulating lipolysis. The 3 distinct subtypes of beta receptors are located in adipose tissue, but they are also located in many other organs: the ß-1 receptor, which is predominantly a cardiac receptor and the target for beta blockers; ß-2 receptor, which is in the lungs (the target of bronchodilating beta agonists) and also found in uterus and skeletal muscle; and ß-3 receptor, expressed primarily in adipose tissue, where it regulates energy metabolism and thermogenesis (turning fat into heat and energy), especially in response to norepinephrine.
Evidence that the ß-3 adrenergic receptors play an active role in weight control in humans comes from the finding that a genetic variant of this receptor constitutes a susceptibility factor for the onset of morbid obesity as well as non-insulin-dependent diabetes. Specifically, this variant of the ß-3 receptor is associated with hereditary obesity in Pima Indians from Arizona and demonstrated an increased incidence in obese patients in Japan. It also exists in non-obese individuals, including a fourth of African Americans and about 10% of the general population in Europe and the United States. Adrenergic lipolysis in human adipose tissue is regulated in a dual nature by adrenoceptors. Most notably, activation of the beta-1, beta-2 or beta-3 subtype increases the process of lipolysis; while activation of alpha-2 receptors diminishes it, (fat cells appear to be the only type of cells in the human body that exhibit such dual regulation by adrenoceptors). Yohimbine, sold as a drug in some other countries, is an extremely potent naturally-occurring alpha-2 receptor antagonist (it blocks this receptor instead of activating it). Studies with this compound have consistently shown that as a result it is capable of increasing lipolysis in humans after oral dosing, via both alpha-2 receptor antagonism and increases in synaptic norepinephrine release. Studies using in situ micro dialysis (i.e. In situ microdialysis measures the chemical composition of the interstitial tissue fluid that is, the fluid to which cells and other target structures are directly exposed) have suggested that a2 adrenoreceptors regulate lipolysis at rest, whereas ß receptors modulate lipolysis during exercise (7). Enhancing lipolysis during a diet is maximized by increasing serum adrenaline, and perhaps glucagon, and decreased insulin concentrations. Testosterone also has some interesting effects on fat cells regulation of beta adrenoreceptors regulation. In adult rats, castration is associated with a decrease in beta adrenoreceptors number combined with a decrease in activity of adenylate cyclase and cAMP production in fat cells. Physiological doses of testosterone to these rats resulted in a restoration of castration and resulted in an increase in beta adrenoreceptors number and increase in hormone sensitive lipase activity (8).
Beta Adrenergic Stimulation White and Brown Adipose Tissue
White and brown adipose tissue lipolysis are mainly under control by the sympathetic nervous system, parasympathetic nervous system activity is very limited (9). As in white fat cells, beta-adrenergic receptor activation in brown fat cells promotes adenylate cyclase activation, cAMP production, and increased lipolysis. Free fatty acids have a dual action: they are used to supply energy through oxidation and to initiate uncoupling of mitochondria possessing UCP with a concomitant increase in heat production. The thermogenesis of BAT is explained by the activity of the mitochondria of brown fat cells, which mostly produces heat instead of ATP when metabolizing free fatty acids (10). Thermogenesis in BAT is mediated by norepinephrine activation of adenylate cyclase activation mediated by sympathetic nervous system stimulation of ß3 adrenergic receptors (11). NE and glucagons play a major role in inhibiting new fat cell formation through the regulation of the S14 gene expression. S14 gene expression causes adipogenesis or creation of new adipose tissue. NE plays a major role in the regulation of this gene as administration of NE causes a 20-fold decrease in S14 gene expression (12). Interestingly, elevation of cAMP also causes a decrease in S14 gene expression.
Forskolin Increased cAMP and Fat Loss
Therefore, if you have grasped anything from the article it should be that increasing cAMP stimulates fat lipolysis. Catecholamines increase cAMP, but interestingly a supplement called forskolin can do the exact same thing without affecting catecholamines (13). Coleus forskohlii is a plant native of India. The active ingredient Forskolin has been isolated from the roots of Coleus forskohlii and has a wide array of health benefits. Forskolin has been used for centuries in Ayurvedic medicine to treat various diseases such as hypothyroidism, heart disease, and respiratory disorders. Additionally, Forskolin has been gaining popularity for its "fat burning" properties. The forskolin in the plant can activate cyclic AMP, which then initiates a cascade of biochemical events that result in everything from fat release to hormone release. Forskolin differs from ephedrine in that it does not interact with beta-receptors in fat cells, so it has none of the stimulation effect associated with ephedrine. In effect, forskolin is a biochemical shortcut as far as fat release is concerned. It is also thought that forskolin may enhance fat loss without loss of muscle mass (14), additionally forskolin does not appear to be associated with any clinical side effects and increases stamina (15). For example, Scarpace et al. (16) reported that when young and old rats were administered forskolin, both groups had increases in whole body oxygen consumption and increased activity of brown adipose tissue thermogenesis. Forskolin administration has been shown to cause a 50% reduction in S14 gene expression (i.e. this gene regulates adipogenesis) (12). In the past year, there has been tremendous debate as to whether Ca+ can reduce adipose tissue. Cell culture studies with fat cells have shown that calcium stored in fat cells plays a crucial role in regulating how fat is stored and broken down by the body. It is thought that the more calcium there is in a fat cell, the more fat it will burn. It has also been demonstrated that increased cellular action of cellular Ca+ levels, which are caused by NE, can be mimicked by forskolin (17). It has also been demonstrated that forskolin in vitro (i.e. in test tube fat cell cultures) has been shown to stimulate lipolysis and stimulate hormone sensitive lipase activity (18). Substances that reduce actions of catecholamines reduce NE induced increases in cAMP. For example, the beta- antagonist propranolol abolished NE increases in cAMP in fat cells (17). Another interesting feature of forskolin is its ability to "sensitize" the a2 adrenoreceptors. For example, in fat cell cultures, adding a a2 antagonist can cause a marked desensitization or down regulation of the receptor, yet adding forskolin can cause a marked sensitization of the receptor. By adding forskolin to a a2 antagonist can cause a 10-20 fold sensitization of the receptor (19).
One other benefit of forskolin use may be enhancement of testosterone levels through its potential influence on cAMP (14). Leutinizing hormone exerts its effects on Leydig cells in the testes through stimulation of cAMP. Through enhanced natural testosterone production caused by cAMP accumulation, Forskolin may decrease fat mass while having an anabolic response. Forskolin, seems like it might be a useful supplement to add in addition to a caffeine/ephedrine stack or stacking it with a thermogenic supplement. Since forskolin does not interact with adrenergic receptors, forskolin will not raise blood pressure. In addition, because forskolin is a postreceptor agent, its effects should not diminish over time. Because of this, forskolin can be used for long periods with no reduction in effectiveness.
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