Secretion of soluble leptin receptors by exocrine and endocrine cells of the gastric mucosa

Abstract

Leptin is a hormone secreted by the gastric mucosa into the lumen of the stomach. It is present in its intact form in the intestine where it regulates nutrient absorption and intestinal mucosa integrity. We have identified the binding protein that protects leptin from the harsh conditions of the gastric juice. Immunoprecipitations and Western blot analyses demonstrated that leptin is present in the gastric mucosa and the gastric juice, bound to a protein corresponding to the extracellular domain of the leptin receptor. In the absence of this soluble receptor, leptin is rapidly degraded. Immunocytochemistry on rat gastric mucosa identified the cells and intracellular compartments involved in secretion of this complex. Leptin receptor extracellular domain and leptin are present along the rough endoplasmic reticulum-Golgi-granules secretory pathways and form a complex in the secretory granules of Chief and specific endocrine cells. The long-form membrane leptin receptor OB-Rb, the protease activator furin, and proprotein convertase 7 were found in Chief cell granules but not in those of endocrine cells. The shedding of the receptor occurs in the immature granules. It is concluded that in the immature secretory granules of Chief cells, furin activates proprotein convertase 7 that, in turn, cleaves the extracellular portion of membrane-bound leptin receptors. Leptin bound to its soluble receptor forms a complex that is resistant to the gastric juice. Endocrine cells, on the other hand, generate a soluble leptin receptor by mechanisms different from those of the exocrine cells.

Salivary Leptin as a Candidate Diagnostic Marker in Salivary Gland Tumors

“…However, as far as we know, leptin oligomers have never been reported to be present in blood serum. The fact that leptin may be secreted in the gastrointestinal tract in the form of dimers was also reported by Cammisotto et al (31 ). We confirmed the presence of leptin in the form of oligimers by using 4 different antileptin antibodies.…”

Luminal leptin inhibits l-glutamine transport in rat small intestine: involvement of ASCT2 and B0AT1

“…Indeed, we have demonstrated that leptin receptor is expressed in both the apical and basolateral membrane of intestinal absorptive cells (3). Other authors also showed that leptin is secreted into the gastric lumen after a meal by pepsinogen-containing secretory granules of chief cells (11), which also contain the leptin-soluble receptor, indicating that this leptin receptor isoform is also released into the gastric lumen (12). Bound to this receptor, leptin remains stable in the gastric juice, despite the severe conditions of pH and proteolytic activity in the gastric lumen, and is able to reach the intestinal lumen (17).…”

“…The Ussing chamber technique mimics the relevant action of leptin, which is produced and secreted by gastric cells (1,11) together with its soluble receptor (12) and can flow along the digestive lumen to reach the small intestine and act as a physiological modulator. In fact, using leptin mutein, a leptin receptor antagonist (26), we demonstrate that this modulation requires an effective interaction of leptin with its specific receptor located at the BBM of the small intestine (3,9).…”

In vivo regulation of intestinal absorption of amino acids by leptin

“…In the same year, another group reported that the chief cells of the stomach secreted leptin into the gastric lumen after a meal (Bado et al 1998). This study was followed by the demonstration that the chief cells also secreted the leptin soluble receptor (Cammisotto et al 2006), and that leptin remains stable in the gastric juices because binding to this receptor protects it from the acidic pH and the proteolytic activity of the stomach, favoring its arrival to the small intestine (Guilmeau et al 2003(Guilmeau et al , 2004. All these results supported our initial discovery about the role of luminal leptin as regulator of intestinal sugar absorption, and were followed by further studies on leptin modulation of sugar transport (Barrenetxe et al 2001, Iñigo et al 2004, 2007, Ducroc et al 2005, Sakar et al 2009).…”