Appetite control is a major factor when it comes to successful weight loss. Hunger is a powerful built in survival drive controlled by the brain. It is difficult if not impossible to subdue your hunger using will power. Many neuro-hormonal signals contribute to a delicate hunger-satiety balance. Among these hormones are ghrelin and leptin, both secreted by the gastric fundus.

The gastric fundus is the ballooning upper part of the stomach. Metabolic surgery like gastric sleeve and gastric bypass procedures are centered on gastric fundus anatomy, structure, and function. Indeed, the gastric fundus is either resected like in gastric sleeve surgery or bypassed in the case of Roux-en-Y gastric bypass procedure. Metabolic surgery is the surgical manipulation of a seemingly normal organ to achieve a biologic effect. When it comes to weight loss, the gastric fundus seems to be that organ. Made of thin, high compliance wall, the gastric fundus stretches following food intake to accommodate a meal. Gastric fundus is well known as a major site for ghrelin synthesis and secretion also known as the hunger hormone. Interestingly, leptin, a satiety hormone, is also secreted by the gastric fundus. Contrary to initial reports, leptin is not only secreted by white adipose tissue. Several studies have shown that leptin is rapidly secreted by gastric fundus glands in response to food intake. Animal experiments have shown a rapid rise in serum leptin levels in response to re-feeding with a concomitant decrease in gastric intracellular leptin levels. Interestingly, leptin is secreted into the gastric lumen bound to a soluble leptin receptor to protect it from proteolysis. The leptin receptor complex empties with gastric content into the duodenum where it attaches to a duodenal enterocyte transmembrane leptin receptor. The complex is trans-cytosed by the enterocyte and moved from the luminal to the basal membrane. At this level, leptin is absorbed into the blood circulation and reaches the hypothalamus to increase satiety, and metabolism independently of adipocyte secreted leptin. Furthermore, leptin act locally in a paracrine fashion and affects nutrient absorption, and intestinal motility.

Gastric leptin favors satiety and weight loss. However, commonly performed bariatric procedures like gastric sleeve and Roux en Y gastric bypass surgery eliminate the role of gastric leptin. This observation has led me to think about leptin secretion preservation following weight loss surgery. What is the potential effect of leptin secretion on short-term and long-term weight loss following a metabolic procedure? Probably for weight loss surgery that bypasses the duodenum like a duodenal switch and gastric bypass procedure, postop gastric leptin secretion most likely has no role. However, for gastric sleeve surgery, the duodenum is preserved. Gastric emptying is accelerated following sleeve surgery but ingested food and other gastric content still interacts with duodenal mucosa. As a result, leptin elimination following gastric sleeve may decrease the amount and durability of post-operative weight loss. A metabolic procedure like gastric fundus invagination, GFI, reduces gastric fundus size, improves gastric emptying, decreases ghrelin secretion but preserves leptin synthesis, secretion into the gastric lumen and interaction with the duodenal mucosa. Preserving leptin function in metabolic procedures that do not bypass the duodenum may improve the durability of post-operative weight loss. GFI is a novel weight loss procedure that achieves this goal. I have demonstrated stable postoperative blood leptin levels in an obese rat model undergoing GFI. Future studies are needed to corroborate this observation.