SPARC: Distinct Patterns of Leptin Secretion Elicited by Electrical Stimulation of Different Stomach Regions in Fasted Anesthetized Rats

Abstract

BACKGROUNDThe discovery that the stomach secretes the hormone leptin, plus the finding that vagal afferents express receptors for leptin, in addition to the recognized role of adipocytes in the secretion of the adipokine, have initiated extensive investigations into leptin’s possible roles in the control of feeding. The gastric secretion of leptin and its binding sites on vagal afferents suggest the possibility that gastric electrical stimulation (GES) might produce leptin secretion and modulate visceral sensory information arising from the stomach and relayed to the brain. Such a pathway might have therapeutic potential for treating GI disorders (gastroparesis, eating disorders, etc.).AIMSTo explore or map defined gastric regional patterns of leptin release, secretion of the hormone to GES at different sites was measured in terms of both amplitude and time course.METHODSIn fasted (18 hrs.), anesthetized (Isoflurane) SD rats (n = 49), patch electrodes were sutured on ventral stomach wall, a strain gauge was attached to duodenum, and a catheter was inserted into left femoral artery. Stimulation (biphasic, 0.3mA, 0.2ms, 10Hz, 20s‐on‐40s‐off; 5 cycles) was applied from 0 to 5 min. The gastric antrum, corpus and forestomach were each divided into three regions corresponding to the distance between the lower esophageal sphincter (LES) and the greater curvature (GC); each of the three gastric compartments (verified post mortem) was stimulated near the LES, at a mid‐point, and near the GC. Multiple blood samples (0.15ml/each) were collected to measure leptin concentrations.RESULTSStimulation of much of the antrum (mid‐and near‐GC antral regions) evoked fast, robust and long‐lasting leptin secretion. Stimulation of the corpus in a more limited area (mid‐corpus) produced moderate, long‐lasting leptin secretion. Stimulation of a limited forestomach area (mid‐forestomach) yielded a mild, short‐interval leptin secretion. For the effective loci, leptin secretion amplitude changes in post‐stim time points of 5, 15, and 30 min, respectively, compared to control values, were: Mid‐antrum: +58%, +70%, +48%; Near‐GC antrum: +43%, +70%, +33%; Mid‐corpus: +25%. +38%, +38%; and Mid‐forestomach: +38%, +22%, +8%.DISCUSSIONGastric leptin is secreted by both exocrine and endocrine pathways. Antrum sensitivity to stimulation may reflect higher density of leptin‐secretory epithelium, corpus may have moderate density leptin‐related epithelium. Without leptin‐related epithelium in forestomach, leptin release may be caused indirectly.CONCLUSIONOur findings reveal that GES in different stomach regions can produce strikingly different leptin secretion patterns. Selectively modulating leptin secretion with GES applied to different stomach regions could be used as a neuromodulation strategy to treat GI disorders such as gastroparesis, obesity, and various eating disorders.Support or Funding InformationFUNDING: SPARC/NIH OT2 OD023847NIDDK/NIH R01 DK027627