Nature: Leptin and energy balance.

Leptin is a hormone secreted by adipose tissue and its content in the serum is proportional to the size of animal adipose tissue. !----leptin acts on receptors located in the central nervous system (Leptin Receptor) to regulate biological behavior and metabolism.when the body fat of the animal is reduced or is low in energy (e.g. hunger), the amount of leptin in the serum decreases significantly, thus stimulating the animal's foraging behavior while reducing its own energy consumption., on the contrary, when the body fat of the organism increases, the amount of leptin in the serum increases, which in turn inhibits eating and accelerates metabolism.leptin regulates the energy balance and weight of organisms through such negative feedback mechanisms.leptin gene (ob) was first cloned in 1994 by a team of Professor Friedman at Rockefeller University.this major discovery, which has led academics to recognize the close link between obesity and genes, and opened a new chapter in scientists' research on obesity, energy metabolism, and neuroendocrinology.mice with leptin deficiency abnormally obese (ob/ob) due to a gene mutation of leptin, because leptin receptors do not receive signals, resulting in a false "zero-fat low-energy state" in the mutant mice.the mice exhibited a strong appetite, and as their energy metabolism and the breakdown of fat were inhibited, eventually accumulating fat several times more than normal mice.further research revealed that by treating the mutant mice with long-term leptin protein, their appetite and metabolism returned to normal and their obesity symptoms eventually disappeared.For more than two decades, although there has been considerable understanding of the relationship between leptin and appetite and metabolic regulation in mice, the specific mechanisms of how leptin promotes fat breakdown and utilization remain unclear.a study published in nature magazines, "A Leptin-BDNF pathway regulating adipose innervation",a team of professors at Rockefeller University," revealing how leptin regulates the distribution of sympathetic nerves in adil tissue, and illustrates the important role of the sympathetic nerve in fat breakdown and use.the study found that in the fat organs of obese mice (db/db) where leptin deficiency (ob/ob) and leptin receptor mutations were mutated, the distribution density of sympathetic nerves was significantly lower than in wild mice.this also prevented the mice from normally breaking down stored fat in their bodies to provide energy for themselves.long-term injection of leptin in adult obese mice can reduce the density of nerve distribution in their fat to normal.it also restores their physiological function of efficiently using fat storage to provide energy for themselves in cold environments and maintain constant body temperature in cold environments. the study is the first to reveal that the density of sympathetic nerve distribution in fat organs is closely related to the physiological function of fat organs. more important is that leptin, secreted by the fat organ itself, can flexibly regulate the distribution density of its own nerves. it is very rare such a large change in neural structure (plasticity) in the organs of adult mice, which is usually only seen in the growth and development of mice or in the repair of damaged tissue. leptin receptors are mostly distributed in a region of the animal's brain called the hypothalamus. to find neurons in the brain that are specifically regulated by leptin and control the distribution of sympathetic nerves, the researchers used pseudorabies virus (pseudorabies virus, PRV) to track central neurons distributed upstream of the sympathetic nerve in fat organs. studies have found that several brain regions in the brains of mice, including the archea nucleus (ARC), are indirectly associated with sympathetic nerves in the fat organs while expressing leptin receptors. by injecting adenovirus (AAV) into the brains of adult mice through stereotactic surgery to regulate the expression of leptin receptors in these brain regions, the team found that the density of nerve distribution in their fat organs was significantly reduced only when the mice were struck off the ARC brain region leptin receptors. there are a variety of neurons in the ARC region that express leptin receptors, two groups of neurons that are particularly important -- the toxoplasma Y/AgRP-associated protein (NPY/AgRP) and the aheptine genitourin (POMC) -- play the opposite role in controlling appetite and metabolism. then the researchers further struck leptin receptors in AGRP or POMC neurons in adult mice using CRISPR-Cas9 gene editing techniques, and then observed changes in the neural structure of the fat inner fat in the mice. interestingly, although the functions of the two types of neurons are very different, any type of leptin receptor that is missing can lead to a decrease in the density of nerve distribution in the fat, resulting in significant changes in the metabolism of mice. , AGRP and POMC neurons of leptin receptors in the archnuclear region of the brain can interact to regulate the distribution and function of sympathetic nerves in adipose tissue. brain-derived neurotrophic factor (BDNF) signaling pathway is also crucial in controlling the body's energy balance. Patients who BDNF or its receptor TrkB mutation will be severely obese. Although the activation of the BDNF signaling pathway in the central nervous system also promotes energy metabolism, the role of this pathway in regulating the neural structure of the fat organ has yet to be discovered. Another bright spot in the is the discovery that the BDNF signaling pathway can regulate metabolism by acting downstream of the leptin signaling pathway. specifically, leptin promotes fat breakdown and use by regulating the nerve structure in the fat organs by regulating the neurons that express BDNF in the paraventic ventricular nucleus downstream. although clinical cases of obesity due to the leptin gene and its receptor gene varianthave have been identified, but such patients in the total number of obese patients accounted for only a small proportion. the vast majority of obese patients have accumulated a lot of leptin due to excess fat content, but because the hypothalamus neurons produce varying degrees of leptin resistance, they cannot lose weight by injecting leptin. the study found that leptin is instructive for clinical research and future drug development by regulating downstream neuronal activity and thus affecting metabolism, revealing the enormous potential for treating obesity by directly targeting these neurons using existing or new drugs. .