What You Don’t Know About Ghrelin

With increasing numbers of the training population turning to evidence-based nutrition and practice, the complexities of the neuroendocrine system are going to become a topic of confusion for many. This isn’t going to change anytime soon. The processes controlled by the neuroendocrine system are as important as any for athletes that want to perform (or look) their best. Although it’s an extremely interesting subject to study, it can be daunting for people looking to get their teeth into the literature to sift out the sense from the nonsense — this is the nature of any subject as dense as the body’s complex systems. To help work through the confusion and lack of reliable, easy-to-understand information on the neuroendocrine system, I am going to look at several various hormones and present literature in a matter that a lay-person will be able to understand. First up: ghrelin.

Contrary to popular belief, the adipose (fat) tissue in the human body doesn’t just store fat. A lot of recent literature has shown that adipose tissue is actually a highly active endocrine organ, which secretes and regulates a variety of hormones, namely ghrelin, leptin, adiponectin and resistin. All of these hormones have been implicated with the regulation of energy metabolism through a number of studies (1). This article will focus on ghrelin, a hormone known to promote feeding and regulate long term energy metabolism. The better you understand it, the more you can use it to your advantage.

History of Discovery

Ghrelin is produced primarily in the fundus of the stomach, with small amounts being produced elsewhere in the body. Its discovery is an interesting story. In 1996 the growth hormone secretagoue receptor (GHSR) was discovered, with expression primarily in the anterior pituitary and hypothalamus (2). Prior to it’s discovery, growth hormone secretaguoes were used to treat children with growth disorders, but the receptor was unknown. The discovery of the receptor paved the way for the discovery of ghrelin in 1999 by a Japanese group (3), which described it’s function as a growth hormone releasing peptide. This should catch your attention: ghrelin is linked to release of growth hormone peptides.

So, what exactly does ghrelin do? As you’ll have guessed from the previous paragraph, ghrelin binds to the GHSR receptor and subsequently mediates the release of growth hormone form the anterior pituitary (4). Most well known is ghrelin’s ability to stimulate appetite. Through that pathway it can rule weight gain or loss; if ghrelin controls appetite, appetite controls food intake, and food intake controls weight gain, we should be paying close attention to ghrelin and how we may be able to manipulate or manage the hormone. It has also been shown to have effects on other parts of the body, due to widespread expression of the GHSR (1).

Although there are various orexigenic (appetite stimulating) peptides such as NPY and AGRP, ghrelin is the only well-established orexigenic hormone. Recent research has lead to the discovery of a hormone called the insulin-like peptide 5 (5), but this is novel research and more work needs to be done to validate its existence and function.
Ghrelin has been shown, via various studies in rodents and in humans to have mass-building effects (but probably not the kind you’re looking for).

It does so primarily by its ability to:

•Stimulate food intake
•Increase fat mass
•Decrease energy expenditure
•Have a role in ‘food reward’ eating behaviour (1, 6)

When is Ghrelin Secreted?

In humans, blood ghrelin concentrations increase before a meal and decrease dramatically after eating (4), suggesting that it may play a role in food anticipation and the hunger sensation. A common misconception is that ghrelin is the “starvation hormone.” Research has shown that during periods of prolonged starvation, ghrelin levels actually drop. Most people reading this will be familiar with David Blaine and his well-publicized 44-day fast. During the entire duration of this fast, Blaine stayed inside a plexiglass case that was hung over the River Thames in London, England. He consumed no food and reportedly drank only 4.5 liters of water each day. After he had completed his stunt, he was observed extremely carefully in the hospital setting, and his serum ghrelin level was noted to be “extremely low.” This defies starvation hormone hypothesis (7). Moreover, another study reported no increase in total secretion of ghrelin after a 61.5 hour fast when compared to a fed control (8).

The Future?

Ghrelin clearly has a very important role to play in the homeostatic energy balance equation. There is a growing body of literature on ghrelin being an important part of the food reward pathway. Studies have shown that ghrelin administration increases the intake of palatable food (and alcohol) in rodents. This makes the ghrelin system an interesting target for pharmaceutical companies as they strive for a ‘magic bullet’ for the global obesity pandemic.

References

1. Meir U, Gressner AM (2004) “Endocrine Regulation of Energy Metabolism: Review of the Pathobiochemical and Clinical Chemical Aspects of Leptin.” Clinical Chemistry.
2. Kokima M (2001) “Ghrelin: discovery of the natural endogenous ligand for the growth hormone secretagogue receptor.” Trends Endocrinal Metabolism.
3. Bowers CY (2012) “History to the discovery of ghrelin.” Methods Enzymol.
4. Wang G (2002) “Ghrelin – not just another stomach hormone.” Regulatory Peptides.
5. Grosse, J et al. “Insulin – like peptide 5 is an orexigenic gastrointestinal hormone.”
6. Darzen DL, Woods SC (2003) “Peripheral signals in the control of satiety and hunger.” Clinical Nutrition Metabolism Care.
7. Korbonits M (2005) “Refeeding David Blaine – studies after a 44- fast.” N Engl J med.
8. Jianhua et al. (2008) “Novel Ghrelin Assays Provide Evidence for Independent Regulation of Ghrelin Acylation Secretion in Healthy Young Men.” The Endocrine Society.