Leptin sensitiv ELISA

The Leptin sensitive ELISA is intended to be used for quantitative measurement of human Leptin in human
serum and plasma samples.

Leptin, the product of the ob gene (1,2), is a recently discovered single-chain proteohormone with a
molecular weight of 16 kD, which is thought to play a key role in the regulation of body weight. Its amino acid
sequence exhibits no major homologies with other proteins (1). Leptin is almost exclusively produced by
differentiated adipocytes (3-5). It acts on the central nervous system, in particular the hypothalamus, thereby
suppressing food intake and stimulating energy expenditure (2, 6-9). Leptin receptors - alternatively spliced
forms exist that differ in length - belong to the cytokine class I receptor family (10-12). They are found
ubiquitously in the body (10, 11, 13, 14) indicating a general role of leptin, which is currently not fully
understood. A circulating form of the leptin receptor exists which acts as one of several leptin binding
proteins (15). Besides its metabolic effects, leptin was shown to have a strong influence on a number of
endocrine axes. In male mice, it blunted the starvation-induced marked decline of LH, testosterone,
thyroxine and the increase of ACTH and corticosterone. In female mice, leptin prevented the starvation-induced delay in ovulation (16). Ob/ob mice, which are leptin deficient due to an ob gene mutation, are
infertile. This defect could be corrected by administration of leptin, but not through weight loss due to fasting
(17), suggesting that leptin is pivotal for reproductive functions.
All these actions may, at least in part, be explained by the suppressive effect of leptin on neuropeptide Y
(NPY) expression and secretion by neurons in the arcuate nucleus (6, 18, 19). NPY is a strong stimulator of
appetite (20, 21) and is known to be involved in the regulation of various pituitary hormones, e.g.
suppression of GH through stimulation of somatostatin (22, 23), suppression of gonadotropins (23) or
stimulation of the pituitary-adrenal axis (21).
The most important variable that determines circulating leptin levels is body fat mass (24-26). Obviously,
under conditions of regular eating cycles, leptin reflects the proportion of adipose tissue (27) showing an
exponential relationship (37). This constitutive synthesis of leptin is modulated by a number of non-hormonal
and hormonal variables. Stimulators in both rodents and humans are overfeeding (28, 29), insulin (3, 5, 30-
33) and glucocorticoids (5, 34-36). Suppression has been shown for fasting (27), cAMP and beta-3-
adrenoceptor agonists (35). From these findings it becomes clear that leptin is an integral component of
various metabolic and endocrine feedback loops (38).
For clinical purposes, it is important to note that serum leptin levels show a moderate circadian variation with
a peak during the night at about 2 a.m. (37). The leptin values at this time are about 30 to 100 % higher than
the levels measured in the morning or early afternoon. This variation together with the influence of food intake needs to be taken into account, when blood samples are collected. Under fairly standardized
conditions, i.e. normal eating cycles and blood sampling in the morning or early afternoon, a single leptin
measurement is informative.
For the appropriate interpretation of measured leptin levels, reference ranges are required. Because body
fat mass is the major confounding variable, these ranges should be referred to measures of the percentage
body fat such as body mass index (BMI) or percent body fat determined by, e.g., bioelectric impedance
assessment (BIA). Leptin levels are higher in females than in males (38,39) and an age dependence was
shown in children and adolescents (40). Therefore, reference ranges referring to measures of body fat
should be stratified according to gender and pubertal development.
Leptin levels are high in most obese patients suggesting the presence of leptin insensitivity
(20,26,37,38,41,42). In a small percentage of patients, however, leptin levels have been found
inappropriately low with respect to their fat mass. It remains for future studies to prove that these patients
represent a new pathophysiologic entity: leptin deficiency. Since leptin has also been shown to be of great
importance for reproductive functions, possible new pathophysiologic mechanisms may be discovered
relating infertility to insufficient leptin production.
The discovery of leptin has released an avalanche of research activities seeking to understand the
regulation and actions of this new hormone. Most importantly, it has provided a key to better understand the
physiology of body weight regulation and to unveil possible pathophysiologic mechanisms in both obesity
and eating disorders. Further, it may provide new insights into certain causes of infertility.
The widespread importance makes leptin an interesting parameter for physicians dealing with metabolic
syndrome, obesity, cachexia and other metabolic disturbances, as diabetologists, endocrinologists,
gynaecologists, andrologists, and psychiatrists treating patients with eating disorders.
The comparison with BMI-related reference ranges may be useful to detect conditions of relative leptin
deficiency as a possible cause of obesity or provide an indication for leptin resistance respectively.
Due to its high correlation with body fat mass leptin measurements under standardized conditions may be
used as a simple and inexpensive test for determination of body fat.
Measuring leptin in anorectic or cachectic patients, young children even in very low concetrations- is also
possible with this kit.
For non-sensitive or normal-sensitive questions (expectation values from 1 to 100 ng/mL, like
measurements in serum or plasma of average people) we recommend our Leptin ELISA, product code
MD53001.