Weight loss by targeting satiety hormone
Aug 27, 2011 - 7:40:40 PM

The number of people who are obese and suffer one or more of its associated health problems (including type 2 diabetes) is escalating dramatically. Researchers are seeking to identify new targets for therapeutics that could limit appetite and thereby obesity. A team of researchers, led by Scott Waldman, at Thomas Jefferson University, Philadelphia, has now uncovered one such potential target by studying the molecular control of appetite in mice.

Guanylyl cyclase 2C (GUCY2C) is a transmembrane receptor that makes cGMP in response to the paracrine hormones guanylin and uroguanylin, which regulate epithelial cell dynamics along the crypt-villus axis. The researchers showed that silencing of GUCY2C in mice disrupts satiation, resulting in hyperphagia. This caused obesity and metabolic syndrome. In the study, Waldman and colleagues found that nutrient intake by mice caused cells in their gut to secrete the precursor of the hormone uroguanylin (prouroguanylin) into the blood. This travelled around the blood and was converted to uroguanylin in a region of the brain known as the hypothalamus, which is well known to be involved in decreasing appetite. The active uroguanylin was then found to bind to proteins on nerve cells known as GUCY2C receptors, triggering a cascade of events that led to decreased food intake.

The uroguanylin-GUCY2C endocrine axis may provide a therapeutic target to control appetite, obesity, and metabolic syndrome.

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