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Anyone, who is even vaguely familiar with gut physiology, by now knows that besides being an exocrine organ (=secreting digestive fluids into the gut lumen), the gut also secretes a vast array of molecules into the blood stream that act at remote areas – simply said, the gut is also an endocrine organ and the term “incretins” is often used to describe the various hormones secreted by the gut.
In this week’s issue of CELL, Matthew Gillum and colleagues from Yale University School of Medicine, New Haven, CT, report that a relatively abundant group of plasma lipids molecules with the unpronounceable name N-acylphosphatidylethanolamines (or better called “NAPEs”) are secreted into the circulation from the small intestine in response to ingested fat and that systemic administration of the most abundant circulating NAPE, at physiologic doses, decreases food intake in rats.
They also showed that NAPE enters the brain and is particularly concentrated in the hypothalamus (a key area in the regulation of hunger and satiety) and that intracerebroventricular infusions of nanomolar amounts of NAPE reduce food intake. Not surprisingly, chronic NAPE infusion in rats results in a reduction of both food intake and body weight, suggesting that NAPE and long-acting NAPE analogues may be novel therapeutic targets for the treatment of obesity.
Thus, we can now add another molecule to the long list of gut-derived hormones that have been shown to affect food intake. While this discovery emphasizes the importance of better understanding gut physiology and how it interacts with the regulation of food intake, we must be cautious of jumping to conclusion that this is the new “magic bullet” for obesity.
The history of obesity pharmacology is littered with promising lead compounds and targets that failed to deliver safe drugs that work – however, every new avenue that holds promise is welcome – if NAPE analogues can be developed and prove to be safe and effective even in a subset of obese individuals, it would represent a major leap forward in our ability to treat this chronic and debilitating condition.
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