Role of leptin as a factor regulating bone metabolism

Discovered in 1994, leptin is one of the most important anorexigenic factors in the body. This hormone is synthesized and released mainly by white adipose tissue, but could also be released by other tissues. Its main function is suppressing the feeling of hunger by interacting with LEPRs receptors located in the hypothalamus, which makes it one of the main factors regulating the food intake. Appetite regulation is not the only function of leptin in the organism. By interacting with LEPRs, it can also influence the metabolism of various body tissues and organs, such as gonads, immune system cells, bone marrow, and bones. A very important aspect of leptin activity, though seldom discussed in the literature, is its impact on bone tissue metabolism. Leptin can affect bone cells through two different pathways: a peripheral one and a central one. The peripheral pathway involves a direct interaction of leptin with LEPRs located on the surface of bone cell. The central pathway, on the other hand, involves the interaction of leptin with structures of the central nervous system, which regulates the secretion of many hormones, such as serotonin, growth hormone, and thyroid hormones, directly affecting the metabolic activity of bone cells. Determining the overall effect of leptin on bone metabolism is not an easy task. This is due to significant differences in the way individual leptin activity pathways may affect bone metabolism. Indirect pathways stimulate bone tissue in bone anabolic or bone katabolic processes, leading to an increase or a decrease in bone mass, depending on the hormone through which bone metabolism is regulated. However, most of the literature data suggest that the leptin regulation of bone turnover is determined mainly by the direct pathway, and the overall effect of its activity is an increase in bone tissue mechanical parameters. Nevertheless, a complete understanding of these mechanisms requires further research. It is worth mentioning that this hormone is also involved in the development of several disorders of the skeletal system, such as osteoarthritis, osteoporosis, and rheumatoid arthritis, but the exact impact of leptin on the course of these diseases is still not fully understood.