That Which Makes You Fat: Ghrelin the Gremlin

Have you ever felt like just eating and eating and eating...and eating for no particular reason? You are not hungry, not depressed, not anxious, you just want to eat. And so you do. Until your stomach swells up like a scared puffer fish. And then afterwards, you sit back and contemplate why the heck you just ate so much (and maybe cry a little bit at the thought of how much gym time it'll will cost you to make up.) I am here to tell you: there's a reason for that.

It's called ghrelin. For many of you, this may be the first you've heard of ghrelin "the gremlin." Ghrelin is the reason you choose cake over carrots and chocolate mousse over broccoli (like I did yesterday). Ghrelin the gremlin is the reason that fasting diets never work. A  hunger stimulating peptide, ghrelin is the scourge of dieters everywhere. Ghrelin is synthesized as a preprohormone; then processed into a 28-amino acid peptide. The third amino acid (usually a serine) is modified by an acyl group. The octanoylation of this third amino acid is responsible for the activity of ghrelin. If octanoylation fails to occur, then the ghrelin remains "unactive". In this form, it is known as desacyl ghrelin. Desacyl ghrelin does not bind to GHSR1a ( variant of growth hormone secretagogue receptor) and thus does not release growth hormone.
Acyl ghrelin, the active form, is known as the "hunger hormone."
Ghrelin is produced in the placenta, kidney, hypothalamus, and pituitary glands of the body; however, the main sources of generation are the P/D1 cells lining the fundus of the stomach and the epsilon cells of the pancreas. Acyl ghrelin works to stimulate the release of growth hormone by interacting with the growth hormone secretagogue receptor in the anterior pituitary (such a long name! we will call it GHS-R.)

Acyl ghrelin also functions to increase the hunger levels and fat mass of the body, by interactions with the hypothalamus. Ghrelin activates the orexigenic neuropeptide Y neurons; thus increasing food intake. Ghrelin levels increase naturally before a meal, and are highest usually in patients who suffer from anorexia nervosa, as periods of fasting also increase ghrelin levels.Test subjects injected with ghrelin reported feelings of "intense hunger." In addition, Ghrelin functions to inhibit fat utilization in adipose tissue.

So it seems like in order to successfully lose weight, the natural course of action would be to attempt to lower ghrelin levels in the body. Less ghrelin means fewer bouts of "hungry fever", right? And that means less body mass. Unfortunately, this equation does not always stand true; and attempting to act upon it may even prove unfruitful. Actually, obese patients tend to have low ghrelin levels, and higher leptin (hormone that promotes feelings of satiation) levels; and as I mentioned earlier, the opposite is true for anorexics.
The ratio of ghrelin to leptin in obese patients indicates successful prospects of weight loss, but also a very low metabolic rate. Attempting to reduce ghrelin levels by missing meals or lowering food intake, will only produce the opposite effect.
The best, and really only way to "control" the ghrelin levels in your body; is to promote feelings of satiation through the types of foods you ingest. If a low calorie diet combined with exercise is the only way to achieve weight loss; but lowering food intake causes ghrelin levels to increase, causing you to actually eat more, then there has to be some way to cheat the system, right? THERE IS. And it's called fiber. Eating foods that are high in fiber or protein will actually leave you feeling fuller, regardless of their potential low calorie count. Grabbing those low calorie fruits and veggies will give you the potential edge you need to finally beat Ghrelin, the hunger gremlin, and achieve healthy weight loss.

References
Smith, Daniel. A Diet's Effects on Ghrelin. 22 April 2011
http://www.livestrong.com/article/426198-a-diets-effect-on-ghrelin/

Ghrelin. 22 June 2012
http://en.wikipedia.org/wiki/Ghrelin

Kangawa, Kenji. Kojima, Masayusa. Ghrelin: Structure and Function. 2005
http://physrev.physiology.org/content/85/2/495.long

Bowen, R. Ghrelin. 11 Oct. 2009
http://www.vivo.colostate.edu/hbooks/pathphys/endocrine/gi/ghrelin.html

Nishi, Yoshihiro; Hiejima, Hirosh; Hosada, Hiroshi; Kaiya, Hiroyuki; Mori, Kenji; Fukue, Yoshihiko; Toshihiko, Yanase; Nawata, Hajime; Kangawa, Kenji;Masayusa, Kojima.  Ingested Medium Chain Fatty Acids Are Directly Utilized for the Acyl Modification of Ghrelin. 27 Jan. 2005
http://endo.endojournals.org/content/146/5/2255.full

Metabolics/Hormones/Ghrelin. 11 Dec. 2009
http://en.wikibooks.org/wiki/Metabolomics/Hormones/Ghrelin

Doheny, Kathleen; Martin, Laura. Hormone Ghrelin Raises Desire for High Calorie Foods 22 June 2010
http://www.webmd.com/diet/news/20100622/hormone-ghrelin-ups-desire-for-high-calorie-foods

Neuropeptide Y. 27 May 2012
http://en.wikipedia.org/wiki/Neuropeptide_Y

Photocredit: Chris Laughlin/Animals Animals-Earth Scenes