The idea of the existence of this hormone called leptin was later confirmed by subsequent studies.
Leptin (from the Greek "leptos", "lean") is a cytokine produced and released by fat cells. Fat, fat tissue, is not an inert mass. Adipocytes produce a multitude of different cytokines, some not yet well known; leptin is only one among many. In fact, changes in fat mass are transmitted to the CNS:
- Decreased leptin levels "communicate" a depletion of energy reserves. The CNS responds to this by decreasing metabolic activity, increasing food consumption and stimulating enzymes responsible for promoting fat storage
- An increase in the level of leptin leads to an increase in metabolism, a decrease in food consumption, restores hormonal balance (thyroid and androgen hormones tend to decrease in response to low leptin levels), stimulates enzymes responsible for lipolysis and glycogen storage .
However, prolonged elevated leptin levels lead to a desensitization of OB-Rb receptors (long-isoform leptin receptors, proponents of leptin activity) in the hypothalamus and to a downregulation of its transport across the blood-brain barrier. (barrier that divides the brain from the blood tissue). The condition is aggravated by poor glucose metabolism, poor glucose tolerance, chronic hyperglycemia, hyperinsulinemia and insulin resistance (hence type 2 diabetes mellitus).
This is observed in obese individuals who have very high blood levels of leptin, but tremendously low within the cerebrospinal fluid (sign of the impossibility of transport of the hormone through the blood brain barrier). In these subjects, even by administering leptin injections it is not possible to improve the "imbalance" since the OB-Rb receptors, located in the hypothalamus, cannot be reached by the hormone or bind to it due to their desensitization.
In other words, the organism responds negatively by "silencing" this increase in the hormone and this leads to an end of the positive activities that this cytokine has on our body. This, as said before, is the case of "obesity in which very high levels of leptin are not" felt "by the" hypothalamus; the causes can be of a genetic nature such as the deficit of the leptin transporter, the absence of OB-Rb receptors or their total insensitivity to the hormone.
On the other hand, in subjects with genetic deficiency of Ob-RNA, the gene that codes for the production of leptin, intravenous intake of this leads to important improvements in their condition. Leptin is therefore the master regulator of the primary functions of the organism; if it communicates an energy loss, each metabolic pathway is slowed down, if it signals a positive caloric "balance", the opposite will happen.
that respond to its deficiency are responsible for the difficulty in getting down and maintaining a low% of fat mass, but everything starts from the fat cells, from that tissue that we thought was useful only as a warehouse and which instead is even more complex than we thought. The positive side however exists; during a low-calorie diet we empty the fat reserves and we get, in addition to a more pleasant physique, a decrease in the levels, both blood and encephalic (in the brain), of leptin; this involves an increase in both the expression and the sensitivity of the OB-Rb receptors and of the transporters of this dear and lowest cytokine.
, or in any case a period of overnutrition, there is a "surge in leptin levels.
There is no need to accumulate fat to increase leptin synthesis and release. It responds to an increase in blood sugar, therefore to a greater availability of glucose and to the activation of the metabolic pathway of hexosamine - the pathway of hexosamine is the metabolic pathway activated when the organism is faced with an excess of energy from amino acids. and glucose in order to convert them into triglycerides. This increase in leptin combined with a greater sensitivity and expression of OB-Rb receptors leads to a better "communication" of its beneficial messages regarding fat loss, glycogen storage in the muscle and the recovery of a certain balance of the thyroid hormone axes and gonadal; in other words, there is a better caloric partition towards lean tissue.
Leptin governs both efferent systems - described above - as the neuropeptides that activate the two efferent nerve pathways respond to it.
- Decreases in leptin levels stimulate the anabolic effector nervous system by inhibiting the catabolic one
- On the other hand, when its levels increase, the opposite occurs: we will have inhibition of the anabolic effector system and stimulation of the catabolic.
In this case "anabolic" means conserves energy and not "muscle mass gain". The increase in leptin levels tends to stimulate nitrogen retention, protein synthesis and the preservation of lean mass, but this only in the first moments. The body does not like waste and if there were no downregulation and desensitization of receptors OB-Rb the energy waste would be immense and certainly the human species would not have survived until today.
and metabolic rate, depends on leptin. It regulates the thyroid and gonadal hormonal axes.
Low leptin levels lead to low T3 levels and low testosterone and estrogen levels. Furthermore, the release of dopamine is directly related to the brain level of leptin. Animals left fasted for a long time show a certain addiction to drugs that stimulate increases in the concentration of dopamine. All this to understand the reason for the difficulty in falling below certain% of fat.
Once such a low level of synthesis and release of leptin has been reached (due to the emptying of adipocytes), the need for food, asthenia due to decreased metabolism, blocking of lipolysis, increased proteolysis and total loss of libido (sexual need), they become impulses so strong that they cannot be controlled.
The same CCK (cholecystokinin), produced by the stomach in response to a meal rich in fats and proteins and which, as a rule, increases the sense of satiety, has no power if the leptin is low, if the primary control does not give the " approval ".
and adrenaline improves the transport of leptin across the blood-brain barrier (the effectiveness of carbohydrate-based reloads is just that)One way to make the most of the benefits of leptin is to alternate periods of low-calorie diet (the greater the calorie deficit, the shorter the time to spend on the diet before a recharge) with no more than 36 hours of base recharge, almost exclusively. , carbohydrates.
The use of drugs that stimulate the dopamine system, the use of ephedrine and other stimulants that increase the level of adrenaline and noradrenaline, can help to mitigate the drop in leptin. However, sooner or later, whether you use "tricks" or not, the drives for survival will become so strong as to be uncontrollable. Avoid throwing yourself into extremely restrictive diets just because you are in a hurry; what you will get later will be just not being able to keep what you have gained (or lost depending on your point of view).
, the nutrients taken play a key role in the degree of synthesis and release of leptin.
Previously we mentioned the metabolic pathway of hexosamine as a strong "stimulant" to the production of leptin. The final product of this pathway, UDP-N-acetyl glucosamine, appears to be the primary message of the "fed state". As a logical response, we will have an increase in the leptin level.
About 2 or 3% of the glucose entering the cells undergoes a transport (or "shift" in technical terms) towards the metabolic pathway of hexosamine; the quantity of UDP-N-acetylglucosamine produced by this pathway indicates the energetic state of the organism. The same insulin, which seems to have no direct role on leptin, stimulates its production and release by forcing the entry of glucose in this path.
Glucose uptake and metabolism are primary factors in regulating the blood level of leptin. Studies in which glycolysis inhibitors (glucose oxidation) were used blocked the normal increase in leptin production in adipocytes exposed to glucose (non-fructose). ); from this we understand how the metabolism of this sugar is essential in this regulation system. Fructose, on the other hand, is responsible for the "increase in leptin levels in guinea pigs, only after 2 weeks (about 1 month and a half for the" man).
Glucose polymers, such as starch, appear to slow down the leptin peak, which can be explained by observing the strong "insulin surge" in response to glucose alone and this implies a greater entry of sugar into the hexosamine pathway.
Lipids, on the other hand, play an "indirect" role. A diet that includes about 80% of calories from lipids and only 3% from carbohydrates tends to lower the production of our dear cytokine, but if we find ourselves in a state of caloric surplus in which carbohydrates and fats share a "fair share of the calories, we will have a leptin peak similar to that observed in calorie excess from glucose alone.
An increase in free fatty acids shifts the product of glucose metabolism, fructose-6-phosphate, from glycolysis to the hexosamine pathway; here is the indirect effect, but only if a large enough "slice" of the energy surplus is left to the carbohydrates.
It is therefore logical that some perplexities arise regarding "low carbs" diets (not necessarily ketogenic, which require a separate discussion). During a phase of a "cutting" diet, therefore with a certain degree of caloric deficit, maintaining a quantity of glycides, let's say around 3 or 4 g / kg of weight, allows to slow down the physiological decrease in leptin. This, according to some, would still be counterproductive if we seek to optimize the loss of fat and the maintenance of muscle mass; keep leptin levels low, then go towards a strong energy deficit and keep the intake of glycides as low as possible. (without going into ketosis, therefore about 2.2 g of carbohydrates per kilo of lean mass), it allows, as previously mentioned, an increase in the sensitivity and expression of OB-Rb receptors; a better response, therefore, when we enter in the "refeed" phase (carbohydrate refill).
This is not the only reason for consuming low carbohydrates during the definition period. Keeping blood sugar low (blood glucose level) allows an increase in the release of fatty acids from adipose tissue. A high level of FFA (free fatty acids) increases insulin resistance.
Read on: Training and Insulin Sensitivity
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