The mechanism of leptin secretion regulation and energy balance regulation

The level of obmRNA in subcutaneous adipose tissue is higher than that in adipose tissue in other parts of the body. Mutations in the obgene can lead to impaired leptin production, resulting in obesity. For example, individuals lacking guanine nucleotide at position 133 of the obgene have extremely low blood leptin levels, a cause of early-onset obesity and pre-pubertal obesity in their genotype. In 1997, Montague et al. identified two 9-year-old cousins ​​with homozygous leptin gene frameshift mutations who exhibited severe obesity. One of the girls was treated with recombinant leptin subcutaneously, resulting in sustained weight loss, primarily due to a reduction in body fat.

Mutations in the ob gene that cause obesity are rare; the vast majority of obese individuals have normal ob genes, indicating that ob gene mutations are not the primary cause of obesity. Leptin and OBR (Leptin receptor): Leptin originates from the Greek word "Leptos," meaning thin or slender. The nomenclature of leptin is somewhat inconsistent; it is also known as leptin, slimming hormone, leptin protein, leptin factor, anti-obesity factor, etc. Leptin is a protein hormone encoded by the obesity gene and secreted by adipose tissue; it is a polypeptide composed of 167 amino acids.

During its secretion from adipocytes into the bloodstream, the N-terminal signal peptide, consisting of 21 amino acids, is cleaved, resulting in a mature protein of 146 amino acids with a molecular weight of 16,000, existing in the bloodstream as a monomer. Regulation of Leptin secretion: Leptin is secreted by white adipose tissue in peripheral tissues. Compared to intraperitoneal adipose tissue, subcutaneous adipose tissue shows higher expression of Leptin mRNA. Many factors can affect leptin secretion, which can be summarized into several categories. Body fat mass.

The higher the body fat mass, the higher the level of leptin in the blood. Plasma leptin levels are positively correlated with body mass index (BMI, kg/m2) and body fat percentage. Leptin secretion exhibits a diurnal rhythm, peaking at night and troughing during the day. Compared to individuals of normal weight, obese individuals show smaller diurnal fluctuations in leptin secretion. Serum leptin levels are also affected by sex; women have serum leptin concentrations 2-3 times higher than men. This sex difference is due to differences in testosterone levels and is unrelated to estrogen levels, as postmenopausal women still have higher serum leptin levels than men.

Age. Age is negatively correlated with leptin levels; the older the person, the lower their leptin levels. Changes in various hormones and bioactive substances along the leptin regulatory circuit. Since leptin is a hormone that regulates energy metabolism, it is also affected by other hormones involved in energy metabolism. For example, glucocorticoids can stimulate adipocytes to secrete leptin and inhibit its central appetite-suppressing effect; adrenaline and thyroid hormones can inhibit leptin production; tumor necrosis factor-α (TNF-α), estrogen, and insulin can promote leptin mRNA expression and increase blood leptin concentration; androgens can inhibit leptin secretion.

Effects of Leptin on the Body: Regulating energy balance. Leptin can reduce appetite, control diet, and increase metabolic rate. Mediators may include NPY and Agouti-related protein (AGRT). Obesity-related factors positively regulated by leptin include: pro-melanocortin (POMC), growth hormone, corticotropin-releasing hormone (CRH), norepinephrine, R-endorphin, and dynorphin; obesity-related factors negatively regulated by leptin include: insulin, glucocorticoids (GC), thyrotropin-releasing hormone (TRH), glucagon-like peptide-1 (GLP-1), somatostatin, serotonin, cholecystokinin (CCK), neurotensin, and ombresin. Acting on the hypothalamus-pituitary-gonadal axis. Triggering puberty and related reproductive and sexual development. Promoting differentiation of bone marrow hematopoietic cells. It can increase peripheral white blood cells.