Leptin in the control of gastric secretion and gut hormones in humans infected with Helicobacter pylori.

BACKGROUND

Leptin, a protein product of obese gene expressed primarily by adipocytes, provides feedback information on the size of energy stores to central OB receptors controlling the food intake, energy expenditure and body weight homeostasis. It has recently been detected in the rat stomach, especially after cholecystokinin (CCK) administration and in human stomach infected with Helicobacter pylori, but its role in gastric secretory functions in humans has not been revealed. This study was designed to determine the involvement of leptin in the control of basal, CCK- and meal-induced gastric H+ secretion and plasma gastrin and CCK levels in humans before and after an eradication of H. pylori.

METHODS

Two groups (A and B) of subjects were used; group A (n = 7), for comparison of the effects of CCK and leptin on basal gastric H+ and plasma hormone (leptin, gastrin and CCK) levels, and group B (n = 6), for studies on the involvement of leptin in gastric secretory and plasma hormonal responses to vagal stimulation and gastric peptone meal before and after H. pylori eradication.

RESULTS

In H. pylori-positive subjects, CCK (12-200 pmol kg(-1) h(-1)) given i.v. caused a dose-dependent increase of gastric H+ accompanied by a dose-dependent rise in plasma CCK and leptin levels. In contrast, leptin administered i.v. in graded doses (5-80 pmol kg(-1) h(-1)) resulted in a gradual inhibition of basal gastric H+ secretion and in adose-dependent increment in plasma leptin accompanied by an increase in plasma gastrin without alteration of plasma CCK level. Following eradication of H. pylori by 1-week triple therapy in group B patients, the infusion of CCK produced a significantly smaller increase in gastric H+ secretion and significantly smaller rise in plasma leptin as compared to those before the eradication. Cephalic phase stimulation of gastric secretion induced by modified sham-feeding in group B H. pylori-positive subjects increased gastric H+ secretion to about 40% of pentagastrin maximum without affecting plasma leptin, gastrin, or CCK level, while gastric peptone meal resulted in the increase in gastric H+ response reaching about 70% of pentagastrin maximum accompanied by a marked rise in plasma leptin, gastrin and CCK. The treatment with a standard dose of leptin (20 pmol kg(-1) h(-1)) failed to affect sham-feeding-induced gastric H+ secretion but reduced significantly the peptone meal-stimulated H+ secretion, while raising plasma gastrin in response to this meal. Plasma CCK under basal conditions and after sham-feeding was not affected, but plasma CCK response to gastric meal was significantly reduced by leptin infusion. Eradication of H. pylori did not affect basal or sham-feeding-induced H+ secretion but resulted in a significant fall in gastric meal-induced H+ and plasma leptin, gastrin and CCK levels.

CONCLUSIONS

1. The gastric meal and CCK enhance the release of leptin in H. pylori-positive patients and this leptin is capable of inhibiting basal and meal-stimulated gastric H+ secretion, while raising plasma gastrin and reducing the plasma CCK levels, and 2) the eradication of H. pylori reduces the postprandial gastric H+ and plasmagastrin responses as well as the release of leptin in response to CCK and meal.