Leptin is a hormone produced by fat cells. Its mission is to send signals to the brain to accelerate fat metabolism and suppress cravings. Leptin directly reaches its target neurons in some structures of the hypothalamus, which makes the regulation of appetite and body weight. Thus, the hypothalamus receives a signal indicating that enough food has been consumed and therefore suppresses the appetite. In chronically overweight, the problem is that hypothalamic leptin signaling is ineffective, and does not act to reduce appetite and stimulate fat breakdown (lipolysis). Scientists call this state the "leptin resistance".
Studies show that the majority of overweight individuals who have difficulty losing weight have varying degrees of leptin resistance, where the leptin has a diminished ability to produce its normal effects on the hypothalamus to regulate metabolism.
The leptin levels are tested in the blood. Patients with common obesity have an elevation of leptin up to 10 times that of normal individuals and in proportion to their weight fat.
This leptin resistance is felt as hunger, so multiple mechanisms are activated to increase the storage of fat, rather than burn fat reserves, as the body tries to compensate the perception of hunger. Resistance to leptin strongly active appetite (by the neuropeptide Y), and radical solutions used by many, such as too low calorie diets, are ineffective in the long run; it is the "yo-yo" diets where a loss of a few pounds, ensues a rapid gain, even more important. How do we explain this?
Mechanisms that are activated to increase the storage of fat are done by means of a decrease of basal metabolism, and therefore that of the thyroid. These mechanisms include diminished TSH secretion, a suppressed T4 to T3 conversion, an increase in reverse-T3, an increase in appetite, an increase in insulin resistance and an inhibition of lipolysis (fat breakdown). These mechanisms may be in part due to a down-regulation of leptin receptors that occurs with a prolonged increase in leptin. The result? Once you are overweight for an extended period of time, it becomes increasingly difficult to lose weight. [Source: Dr. Kent Holtorf, MD, a California-based expert on hormonal medicine]
The fact that resistance to leptin stimulates the formation of reverse-T3 deserves that I focus again on the reverse-T3.
We know that thyroid hormones regulate metabolism and the low production of thyroid hormones (hypothyroidism) causes low metabolism. We also now know that the production of thyroid hormones can be quite good, accordingly with a TSH in the standard, but that it is the activation of hormones inside the cells that presents a problem. Moreover, this problem can be a major cause of low metabolism. Normally, the hormone T4, an inactive pro-hormone, is converted within cells in equal proportion, or nearly, in active hormone T3, which does the "job", and in reverse-T3, the latter serving to eliminate the T4. A defect in conversion of T4 to T3, whatever the cause, not only reduces the amount of T3 but significantly increases the proportion of reverse-T3. The reverse-T3, an inactive hormone, is a mirror image of T3. It will occupy the T3 intracellular receptors, and, therefore, it will block the effects of the hormone T3. Thus, reverse-T3 causes the opposite effect of the hormone T3 by decreasing rather than increasing the metabolism.
The reversing mechanism is activated in times of famine and in animals that hibernate, to reduce metabolism. Studies show that diets (especially diets that cause the effect "yo-yo") put this reverse-T3 hormone into action. The production of reverse-T3 is one of the main means used by the body to "try" to regain the lost weight after dieting. Once the body detects a calorie reduction, production of reverse-T3 is started to decrease the metabolism. With recurrent regimes (on and off diets), the body stays often in this "starvation mode", with high levels of reverse-T3 hormone and decreased levels of hormone T3; this is one of the main reasons for the recovery of lost weight with diets.
Thus, in people who are overweight or obese, the thyroid function is impaired due to high leptin levels (leptin resistance). However, elevated leptin also indicates that TSH is an unreliable marker for tissue thyroid levels, as the TSH is often suppressed, along with significantly reduced T4-to-T3. In short, if your leptin is elevated, you have reduced tissue thyroid levels.
This proves once again how the circulating TSH and T4 do not reveal the cellular function of the thyroid. Testing a ration T3 /reverse-T3 would be most useful. Generally, a healthy person will have a ratio greater than 2. An individual with a ratio less than 2 should be considered a candidate for thyroid hormone replacement therapy. Which kind of treatment? I discuss later.
Also, almost all diabetics have a resistance to leptin, which has been shown to reduce T4-to-T3 conversion in diabetics by as much as 50 %, without an increase in TSH, making it very difficult for type II diabetics lose weight. The chronic fatigue syndrome and fibromyalgia are also affected by a reduced T4-to-T3 conversion, explaining that a large number of these patients have hypothyroid symptoms, with a TSH in the standard. This is not surprising, since researchers have shown that poor leptin signaling affects the immune system and can be a trigger for autoimmune diseases.
What are others reasons for a hypothyroid patient to make too much reverse-T3 hormone? On top of chronic stresses, there are common physiological reasons related to adrenal glands (low cortisol, known as adrenal fatigue – described below), to low iron and low vitamin B12 levels. Chronic inflammation and other health issues can as well cause it.