High levels of hunger-blocking gut protein may underlie benefits of surgery

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A new study provides insights into a ghrelin-blocking protein that may underlie metabolic benefits of gastric sleeve surgery.
American researchers at NGM Biopharmaceuticals uncovered the benefits of the protein while exploring the effect of sleeve gastrectomy on the hunger hormone ghrelin.
People with type 2 diabetes and those who are obese have a ghrelin imbalance. Ghrelin is implicated in eating disorders, weight regain and altered brain responses to food cues.
Studies have also linked ghrelin to reduced hepatic insulin sensitivity and impaired glucose-induced insulin secretion.
Previous research suggested that the anti-obesity effects of vertical sleeve gastrectomy are mediated by reductions in levels of ghrelin.
In the new study, the NGM scientists investigated changes which occur in gene expression related to ghrelin following vertical sleeve gastrectomy in obese mice.
This type of surgery involves the removal of the gastric epithelium, which is the primary source of ghrelin-producing cells. Researchers also identified another possible cause for reduced ghrelin levels.
They noted that the procedure led to higher expression of a gene coding for a protein found in the liver and small intestine called LEAP2. The stomach of the animals produced unusually high levels (52 times more) of LEAP2 following surgery.
LEAP2 is rich in the amino acid cysteine, which suppresses ghrelin and reduces appetite in rodents – and possibly in humans as well. LEAP2 may also indirectly inhibit ghrelin by disabling a receptor for ghrelin, according to the new research.
There is evidence that suppressing ghrelin and its receptor at the same time decreases body weight and improves metabolism in mice.
In addition to this, the study shows that injecting mice a shot of LEAP2 prevented a rise in growth hormone which in turn prevents the synthesis of glucose in the body.
The team also found that genetically modifying calorie-restricted mice to produce three times the normal amount of LEAP2 led to a significant reduction in blood glucose levels after only a week.
Overall, this study offers insights into a ghrelin-blocking compound that brings on metabolic benefits of weight loss surgery and could be used in new treatments for diabetes and obesity.
The findings were published in the journal Cell Metabolism.