The role of various endocrine hormones and leptin in obesity

Adrenal glucocorticoids: Adrenal glucocorticoids are hormones secreted by the zona fasciculata of the adrenal cortex, primarily in the form of cortisol in the human body. Simple obesity may present with some degree of adrenal hyperfunction, with normal or elevated plasma cortisol levels; however, in secondary obesity, Cushing's syndrome shows significantly elevated plasma cortisol. This elevated plasma cortisol leads to elevated blood glucose, which in turn causes elevated insulin levels. The latter results in excessive fat synthesis, leading to obesity. Because the adipose tissue in the trunk and limbs responds differently to insulin and cortisol, central obesity is observed.

Growth hormone (GH): GH is a protein hormone secreted by the anterior pituitary gland. It promotes protein synthesis, mobilizes stored fat, and has anti-insulin effects, but in the early stages of its action, it also exhibits insulin-like effects. GH and insulin have antagonistic effects in the regulation of glucose metabolism. If growth hormone levels decrease, insulin's effect becomes relatively dominant, leading to increased fat synthesis and obesity. It has been confirmed that obese individuals have lower basal growth hormone levels, and their secretory response is also low under stimuli such as arginine, hypoglycemia, starvation, and physical activity.

As a result, during periods of hunger and physical activity, a significant amount of energy cannot be derived from fat breakdown. For example, after a two-day fast, plasma growth hormone levels rise from 10 micrograms per liter to 15 micrograms per liter in normal individuals, while rising from 2 micrograms per liter to 5 micrograms per liter in obese individuals. This change returns to normal as obesity disappears. Thyroid hormones: The relationship between thyroid hormones and obesity is unclear. Obese individuals generally do not have thyroid dysfunction; even if their basal metabolic rate is slightly lower than normal, it does not necessarily indicate hypothyroidism. Occasionally, both conditions are observed simultaneously.

Sex hormones: In men, the main hormone is testosterone, with over 90% synthesized and secreted by the testes. In women, a small amount is synthesized and secreted by the ovaries and adrenal cortex. Estrogen and progesterone are mainly synthesized and secreted by the ovaries. Sex hormones themselves do not directly affect fat metabolism. Women have more body fat than men, and the percentage of body fat in women is significantly higher than in men. Subcutaneous fat, except in a few areas, is generally twice as thick in women as in corresponding areas in men. Obesity can occur during pregnancy, menopause, and in men or male livestock after castration.

However, the mechanism is still unclear. Some believe that postmenopausal obesity is related to excessive secretion of pituitary gonadotropins. In castrated animals, the pancreatic islets hyperplasia and hypertrophy, leading to increased insulin secretion and promoting fat synthesis. Except for a few cases of hypogonadism-related obesity, generally obese individuals do not exhibit sex hormone secretion disorders. Glucagon: Glucagon is secreted by pancreatic α cells, and its function is opposite to insulin, inhibiting fat synthesis. Whether glucagon levels are disordered in obese individuals requires further investigation. Catecholamines: Catecholamines are produced by the brain, sympathetic nerve endings, chromaffin tissue, and primarily the adrenal medulla.

It can promote fat breakdown. The cerebral cortex regulates hypothalamic function through catecholamines and serotonin, and the sympathetic nervous system regulates insulin secretion through catecholamines. Obese individuals' adipose tissue is insensitive to the effects of catecholamine hormones, but this sensitivity can be reversed after weight loss. Leptin and obesity. Before the discovery of leptin, it was speculated that a signaling protein might exist in the human bloodstream, through which the central nervous system could regulate the amount of fat stored in the body. In 1950, Ingalls et al. discovered that obesity in an inbred mouse strain was caused by a recessive mutation in a gene.

This gene was subsequently named the obesity gene. In 1994, Zhang et al. successfully cloned the obesity genes in mice and humans and identified the protein they expressed, which was named leptin. From then on, it was recognized that leptin is the satiety signal connecting the peripheral and central nervous systems. The discovery of the obesity gene and leptin ushered in a new era in obesity research, truly ushering in the molecular age. Leptin gene (obesegene, obgene): The human leptin gene is a single gene, 18–20 kb in length, located at 7g31.3.

It contains 3 exons and 2 introns (10.6kb and 2.3kb, respectively), with exons and introns linked by GT/AG. The 5' flanking sequences include a TATA box, a GC box, and several cis-acting components, including 3 CEBP binding sequences, 1 E box, and 1 AT2 binding region. The ob-gene can be expressed in various tissues but exhibits some tissue specificity, with the strongest expression in adipose tissue. Its expression is correlated with the fat content of body tissues. The expression level of obmRNA varies among individuals and also differs between different adipose tissue locations within the same individual.