Identification of Leptin in Human Saliva

Abstract

Leptin is produced predominantly in adipose tissue but has recently also been found in gastric mucosa. It has been shown that the oral application of leptin induces neuronal activity in the brain stem of rodents. The objective of the present study was to identify this hormone in human saliva and to examine the production and stability of salivary leptin. We have demonstrated production of leptin in salivary glands and oral mucosa by RT-PCR, its storage by immunocytochemistry, and the release of the peptide by RIA . Chromatographic analysis and immunoblotting confirmed the identity of leptin. There is a strong linear correlation (r 2 ‫؍‬ 0.78) between leptin concentrations from simultaneously collected saliva and plasma samples (n ‫؍‬ 61). Stimulation of saliva flow increases total leptin secretion up to 3-fold (P < 0.001). As to the stability of leptin in gastric fluid, we found the peptide was not degraded above pH 3. S INCE THE DISCOVERY of leptin in 1994, research activities have been directed at understanding the regulation and actions of this peptide hormone. Leptin is the product of the obese gene with a single-chain structure and a molecular mass of 16 kDa. It is produced by differentiated adipocytes (1, 2) as well as in the placenta (3, 4). More recently, storage and secretion of leptin has also been demonstrated in the stomach (5-7). The signal function of leptin on the central nervous system has been the major area of research (8 -12). Leptin influences food intake (e.g. by suppressing neuropeptide Y in the hypothalamus [11], and stimulates energy expenditure and thermogenesis (e.g., by interaction with the adrenal cortex [13,14]). However, specific receptors for leptin have been found ubiquitously in the body (e.g., thyroid gland, adrenal glands, lung, placenta, kidney, liver, and endothelial cells [15][16][17]). This suggests a peripheral role for leptin. Interestingly, a specific leptin receptor was recently identified in the gastric mucosa (6) and in other parts of the gastrointestinal tract (18). To date, the sources of leptin as a gastrointestinal receptor ligand have been only partially investigated.It was therefore an objective of the present study to identify and characterize the presence of leptin in saliva. A second aim was to investigate the regulation of leptin in the salivary glands and its stability under gastric conditions. Materials and Methods Sample materialPlasma and saliva were collected simultaneously from healthy adult males (n ϭ 23; age 28 -80 yr; body mass index [BMI] 20 -50 kg/m 2 ) and females (n ϭ 25; age 22-85 yr; BMI 19.5-54 kg/m 2 ) and healthy adolescents (male: n ϭ 13; female: n ϭ 5; age 10 -18 yr; BMI: 15-39.9 kg/m 2 ) recruited in our hospital, who gave informed consent of participation. None of the volunteers took medication or contraceptives and all participants had fasted for at least 2 h. The study was approved by the Ethics Review Board of the University of Erlangen.Plasma was collected with S-Monovettes, saliva was collected with the Salivette device (both Sarst...

Differential distribution and expression of leptin and the functional leptin receptor in major salivary glands of humans

“…Recently we demonstrated the expression of leptin by the human salivary glands (Gröschl et al 2001). Other authors have shown a direct atrophic effect of leptin on the salivary glands of rats (Higa et al 2002).…”

“…The recent discovery of both leptin and leptin receptors in the stomach (Bado et al 1998, Cinti et al 2000 and the presence of leptin in saliva (Gröschl et al 2001) has led to further questions about peripheral leptin actions, which may influence food uptake, digestion or mucosal proliferation in a still unknown manner.…”

Salivary leptin levels in normal weight and overweight individuals and their correlation with orthodontic tooth movement

“…[7][8][9][10][11][12]16 This study sought to assess the concentration differences of leptin in saliva between normal weight and overweight individuals and its correlation with orthodontic tooth movement. An association was found in this study between salivary leptin levels, BMI, and orthodontic tooth movement.…”

“…[2][3][4][5][6] Leptin is a 16-KDa, nonglycosylated polypeptide hormone produced primarily by adipocytes and in minor quantities by the placenta, stomach, osteoblast, and salivary glands. [7][8][9][10][11][12] There is a strong positive correlation between serum leptin concentration and body mass index (BMI) or fat mass. [13][14][15] Leptin plays a dual role as a hormone and cytokine.…”

“…28 Leptin is also expressed in saliva, and there is a strong positive correlation between leptin concentration from saliva and serum samples. 11 Analysis of leptin in saliva is noninvasive, and its concentration is high compared with plasma samples. 12 Orthodontists are in a unique position to see children and adolescents over a significant period of time.…”