1, appetite suppression: Leptin can significantly reduce human food intake, weight and body fat content.
2. Increase energy consumption: Leptin can act on the central nervous system, increase sympathetic nerve activity, and convert a large amount of stored energy into heat energy for release.
3. Effect on fat synthesis: Leptin can directly inhibit fat synthesis and promote its decomposition. Some people think that it can promote the maturation of fat cells.
4. Effect on endocrine: Insulin can promote the secretion of leptin, and then negatively regulate the synthesis and secretion of insulin. The level of leptin in plasma is usually positively correlated with the changes of body weight, especially the adipose tissue in the body, which leads to leptin resistance and negative myocardial muscle strength. Clinically, the serum leptin level of obese patients often increases to varying degrees. Because the normal physiological function of leptin is mainly mediated by leptin receptor, the increase of leptin level in obesity directly leads to the feedback reduction of leptin receptor level or the obstruction of signal transduction after leptin receptor, which is called leptin resistance.
The emergence of leptin resistance is directly caused by the increase of circulating leptin level. To make a very appropriate analogy, the status of leptin resistance in obesity is similar to that of insulin resistance in type 2 diabetes. Leptin at physiological level can cause vasodilation and has no obvious effect on myocardial function, while leptin at pathological level can promote the production of a large number of oxidative free radicals, which in turn has obvious negative effects on myocardial muscle strength. There is evidence that the negative inotropic effect of leptin at pathological level may be realized by activating endothelin receptor (ET- 1 receptor) and its downstream reduced coenzyme II (NAPDH) oxidase. The activation of NAPDH oxidase directly produces a large number of superoxide anions. These results have been confirmed in the db/db mouse model with leptin excess. It leads to insufficient regulation of leptin on cardiac function at physiological level, resulting in myocardial hypertrophy and low cardiac function, which is contrary to the upward adjustment of leptin level. The decrease of leptin level can also directly lead to the loss of leptin signal transduction, which leads to the loss of leptin's regulation of heart function at physiological level. The author's laboratory has made an in-depth study on ob/ob obese mice with hereditary leptin deficiency. The results showed that low leptin level resulted in obvious obesity (twice the weight of wild-type mice), myocardial hypertrophy, decreased myocardial contractility, slow contraction/relaxation rate, prolonged relaxation time, calcium regulation of myocardial cells and other cardiac dysfunction in mice. Interestingly, leptin supplementation can significantly improve myocardial hypertrophy and cardiac dysfunction caused by leptin deficiency, while significantly inhibiting weight gain.
Further research results show that low leptin level directly leads to the decrease of insulin sensitivity. In 2007, the author's laboratory changed the structure of chromium complex, an insulin sensitizer, and obtained a new chromium amino acid complex (patented in the United States). We use this complex to sensitize obese leptin deficiency in obese mice. After oral administration of [45 μ g/(kg/d)] for 6 months, the myocardial function of ob/ob mice was obviously improved, and the disorder of intracellular calcium regulation was corrected, which was consistent with the improvement of myocardial insulin sensitivity. From this point of view, whether the leptin level is increased or decreased, it will lead to the disorder of leptin regulating energy and fat metabolism, thus contributing to obesity and eventually leading to type 2 diabetes. However, high-fat diet or overnutrition can lead to a sharp increase in leptin levels, and the resulting leptin resistance prevents leptin from promoting fat and energy metabolism and its related appetite suppression.
Leptin has a two-way effect on body weight regulation in vivo, which is usually called body fat homeostasis system. It can be understood that when the energy intake of human body is in a positive balance, body fat increases and promotes the secretion of leptin by fat cells. Leptin acts on hypothalamus and binds to its receptor, resulting in satiety reaction, thus reducing appetite, reducing energy intake and promoting energy consumption; When human body loses weight, leptin secretion in adipose tissue decreases, which acts on another receptor in hypothalamus, resulting in hunger reaction, increased appetite, increased food intake and reduced energy consumption. Accordingly, the human body weight should be kept within the normal range. Why are more and more obese people? This is the leptin resistance problem. Although leptin is secreted a lot, it can't play a role. The serum leptin level of most obese people is higher than that of non-obese people. Less than 5% of obese people lack leptin. The most regrettable thing is that obese people not only have resistance to leptin in vivo, but also have resistance to exogenous leptin. Therefore, the application of leptin in the treatment of obesity is still in the experimental stage.