| Leptin is a 167 amino acid protein encoded by the ob gene. It has been found that leptin is produced for the most part in white adipose tissue, with very small amounts being found in brown adipose tissue. Leptin is a four-helix bundle with one very short strand segment and two relatively long interconnected loops. This is consistent with a classification as a cytokine four-helix bundle. Leptin is a protein expressed by the ob gene. Leptin is secreted by adipose tissue and appears to be both a satiety factor and a
regulator of metabolism. Small amounts of leptin are also secreted by cells in the epithelium, stomach and placenta. Leptin is a protein hormone with important effects in regulating body weight, metabolism and reproductive function.
The primary role of leptin is to prevent obesity via regulating food intake and thermogenesis via action on hypothalomic centers. Leptin appears to be a sensor of fat cell size, so that when the cell reaches a certain proportion, it sends a signal that elicits some metabolic response to eliminate fat. Leptin may also exhibit antisteatotic activity, in that fatty acid over-accumulation in non-adipose tissue may be prevented by leptin mediated regulation of .beta.-oxidation. Leptin increases enzymes involved in fatty acid oxidation and stimulates a previously unobserved form of lipolysis, where glycerol is released without proportional release of free fatty acids. Leptin binds to receptors in the hypothalamus region of the brain. This region influences the gastroenteric reflex. Normal leptin levels damp down production of a brain peptide called corticotropin-releasing hormone that works throgh the pituitary gland to boost production of adrenal steroids. Leptin has been linked to other hormonal functions as well. Leptin appears to signal the onset of puberty.
Leptin works by inhibiting the actions of neuropeptide Y (NPY) and agouti-related peptide (AgRP) and by increasing the actions of alpha-melanocortin stimulating hormone (α-MSH). Leptin counteracts the effects of neuropeptide Y. It counteracts the affects of anandamid. Leptin promotes the effects of alpha-MSH a appetite represent. It also stimulates secretion of reproductive hormones such as gonadotrophin-releasing hormone and thus leutenizing and follicle stimulating hormone from the anterior pituitary. Leptin raises the temperature of the subject so energy expenditure is increased. Neuropeptide Y (NPY), abundant in the hypothalamus, is responsible for the feeling of hunger. The expression and release of NPY is inhibited by leptin. Leptin serves as an intracellular messanger as well. The amount of leptin in the body will directly influence the amount of leptin that is produced by adipose tissue.
Leptin's effects on body weight are mediated through effects on hypothalamic centers that control feeding behavior and hunger, body temperature and energy expenditure. Obesity, defined as an excess of body fat relative to lean body mass, is associated with numerous, important clinical and psychological morbidities, the former includes, but is not limited to: hypertension, elevated blood lipids, and Type II or non-insulin-dependent diabetes mellitus (NIDDM), and decreased life expectancy. Human obesity is more closely linked to leptin resistance than to the absence of leptin. The leptin levels generally correlate with the basal mass index (BMI). As BMI increases, the leptin level increases also. The circulating leptin informs the brain of body fat. Leptin promotes weight loss by suppressing appetite and stimulating metabolism. Leptin decreases meal intake, augments satiety (makes you feel full), and increases the synthesis of uncoupling proteins. As weight is gained the leptin levels are increased. This inhibits the function of NPY creating a response to obesity. Leptin is used for body mass and energy expenditure, but is also involved as a regulatory molecule in lipid metabolism, hematopoiesis, insulin action, reproductive function, immune function, and angiogenesis. In approximately five percent of the population, the leptin level does not reflect the BMI. |
