One of the main reasons why humans become hungry is because of the hormone ghrelin. Ghrelin is primarily secreted by the stomach, which responds to hunger and starvation. Once ghrelin gets into the blood, it circulates the body until it reaches the Vagus nerve, which sends a signal to your brain that tells you “I am hungry!” Actually, for people who have had their Vagus nerve divided (a Vagotomy), ghrelin no longer has a significant impact on hunger. This finding suggests that the Vagus nerve and ghrelin are needed for maximum stimulation of hunger. Also, ghrelin containing neurons are found in the arcuate nucleus, a region of the brain that regulates appetite. In order to stimulate hunger, these neurons send signals to other neurons that contain neuropeptide Y (NPY), which stimulates hunger. However, if the body wants to suppress hunger, it will send signals to neurons containing proopiomelanocortin (POMC). (i)
Now that we know a little about how ghrelin makes us hungry, lets see how the hormone leptin makes us full. Leptin is made in the fat cells (adipose tissue) of our body. The way leptin regulates hunger is by stimulating or not stimulating nerves in the brain. Just like ghrelin, leptin acts on the arcuate nucleus. When leptin is not present, NPY causes us to be hungry. When leptin levels are high, they block NPY and stimulate POMC nerves in the brain that make us full. However, one might ask, if we have more fat cells that produce leptin, why are we still hungry? The answer is that many obese individuals have genetic defects that block the function of leptin. The other is that too much leptin can cause negative feedback to fat cells, which tell the body “hey we have too much leptin, stop making it.” (ii)
Although the exact mechanisms of how ghrelin and leptin work are extremely complex, we see that the three main responses that are contributed to the presence of ghrelin (iii) (iv) are:
- Stimulation of appetite
- Reduction of metabolism
- Reduction of fat catabolism (fat breakdown)
In contrast to ghrelin, leptin’s main responses are:
- Suppression of appetite
- Increase in metabolism
- Increase immune function
The following table summarizes the information on ghrelin and leptin, its relationship with other GI hormones, and its levels after Sleeve Gastrectomy. (v)
Hormone | Source | Mechanism of action in Obesity | Effect on Weight regulation | Levels after Sleeve Gastrectomy |
Ghrelin | Stomach Fundus (mainly), Pancreas, small intestine (vi) | Stimulates Growth Hormone release, stimulate NPY, inhibits POMC, and opposes Leptin action | Stimulates Appetite, Reduces metabolic rate, and reduces fat catabolism (breakdown) | Reduced |
PYY (peptide tyrosin tyrosine) | Is released by endocrine cells of distal ileum, colon, and rectum(vii) | Binds to NPY receptors, inhibits gastric motility, increases water and electrolyte absorption in the colon (vii) | Reduced appetite | Increased |
Leptin | Fat cells (adipose tissue) | Inhibit NPY and activates POMC | Suppress Appetite | Reduced |
By: Chris Tashjian BS – Ara Keshishian MD, FACS, FASMBS
(i) Sato T, Nakamura Y, et al. Structure, regulation, and function of Ghrelin. Journal of Biochemistry. Oct 31, 2011.
(ii) Friedman JM, Halaas JL. Leptin and the regulation of body weight in mammals. Nature. 1998 Oct 22; 395 (6704): 763-70
(iii) Le Roux CW, Aylwin SJ, Batterham RL, et al. Gut Hormone profiles following baraitric surgery favor an anorectic state, facilitate weight loss, and improve metabolic parameters. Ann Surg. 2006; 243:108-114.
(iv) Hansen TK, Dall R, Hosoda H. et al. Weight loss increases circulating levels of ghrelin in human obesity. Clin. Endocrinology 2002; 56:203-206
(v) Melissa Gianos, et al. Understanding The Mechanisms of Action of Sleeve Gastrectomy on Obesity. Bariatric Times 8;5: S4-S6 (Supplement)
(vi) Ariyasu H, Takaya K et al. Stomach is a major source of circulating ghrelin, and feeding state determines plasma ghrelin-like immunoreactivity levels in humans. J Clin Endrocrinology Metabolism. 20001;86:4753-4758
(vii) Liu CD, Aloia T, et al. Peptide YY: a potential proabsorptive hormone for the treatment of malabsorptive disorders. American Journal of Surgery. 1996 Mar; 62(3) 232-6.
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