Are you trying to follow a diet but you always feeling hungry? This is because your body is going through an unusual starvation situation. This appears to profoundly affect your energy metabolism and it is, unfortunately, one of the causes of the yo-yo effect that you so much hate. Multiple hormones that regulate your appetite seem to be involved in this undesired effect. However, The appetite hormone landscape is more complex than previously thought. Here I explain to you two hormones you may have not heard about.

When we eat, the sugars contained in food are absorbed in the intestines. In particular glucose triggers the production of insulin in our pancreas, which activates several molecular mechanisms to absorb this sugar. glucose is then stored in long chains called glycogen. We can only store a limited amount of glycogen, so the excess of glucose goes to…exactly, to our friend fat. But how do we know when have we eaten enough? Besides the feeling of a having a full stomach, several hormones are released to make us feel satiated. One of the most important is leptin liberated by our fat cells called adipocytes. It works something like that: the more fat we have, the more leptin is produced as stop signal 1.  There are more hormones, though.

 The gut hormone GLP-1

holst-auditorium.jpgAs I explained above Insulin is secreted when we eat in order to absorb glucose. It turns out that other hormones can also increase insulin production and at the same time act as signals of satiety. GLP-1, which stands for Glucagon-Like Peptide 1, is released in the presence of nutrients by one type of intestine cells called L-cells 2. One of the first to describe the physiological effects of this important hormone was, in fact, a Danish scientist, the professor Jens J. Holst, who has even deserved an auditorium with his name for this contribution to science. Currently different analogs of GLP-1 are being developed to treat type 2 diabetes a disease characterized by a gradual loss of the ability to release insulin, strongly related to obesity.

This hormone does not only stimulate the production of insulin to regulate your glucose levels but also appears to inhibit our appetite3. It is still unclear how but seems like GLP-1 eventually reaches the appetite controlling region of the brain making us feel satiated. Interestingly some studies also show that exercise after a meal may help increase GLP-1 levels stimulating the production of insulin and facilitating further glucose uptake4. This is another argument that exercise in combination with an appropriate diet is an ideal way to prevent some diseases and to help meeting your health goals5.


LCN2 a new bone-derived hormone

Researchers have also bone up on the endocrine functions of other tissues. For example, bone has been recently investigated as a possible player in regulating the energy metabolism and food intake our organism 6. In this line, a new study has shed light on the mechanisms of this possible function by bone tissue. Researchers demonstrated in a new study that a hormone called LCN2 (lipocalin 2), is released by specialized cells of the bone tissue (osteoblasts) 7. This is very surprising because even though was previously suggested that bones could regulate energy metabolism, there was no definitive evidence of a hormone.


It turned out that engineered mice lacking the gene encoding for LCN2 gained substantially more weight than control animals because they ate more. As demonstrated in the experiments, the presence LCN2 caused appetite reduction in both obese and lean mice. And it does seem that diabetic patients have also less hormone circulating in their blood 7. But how does LCN2 keep you satiated? Researchers were able to track the path of the hormone all the way up to the brain, where is capable of crossing the blood-brain barrier and activate the appetite-regulating region of our brain. Shall we pay more attention to our bones from now on to stay healthier?


1              Ahima, R. S. et al. Role of leptin in the neuroendocrine response to fasting. Nature 382, 250-252, doi:10.1038/382250a0 (1996).

2              Holst, J. J. Glucagon-like peptide-1: from extract to agent. The Claude Bernard Lecture, 2005. Diabetologia 49, 253-260, doi:10.1007/s00125-005-0107-1 (2006).

3              Flint, A., Raben, A., Astrup, A. & Holst, J. J. Glucagon-like peptide 1 promotes satiety and suppresses energy intake in humans. The Journal of clinical investigation 101, 515-520, doi:10.1172/JCI990 (1998).

4              Martins, C., Morgan, L. M., Bloom, S. R. & Robertson, M. D. Effects of exercise on gut peptides, energy intake and appetite. The Journal of endocrinology 193, 251-258, doi:10.1677/JOE-06-0030 (2007).

5              Weiss, E. P. et al. Calorie Restriction and Matched Weight Loss From Exercise: Independent and Additive Effects on Glucoregulation and the Incretin System in Overweight Women and Men. Diabetes care 38, 1253-1262, doi:10.2337/dc14-2913 (2015).

6              Lee, N. K. et al. Endocrine regulation of energy metabolism by the skeleton. Cell 130, 456-469, doi:10.1016/j.cell.2007.05.047 (2007).

7              Mosialou, I. et al. MC4R-dependent suppression of appetite by bone-derived lipocalin 2. Nature, doi:10.1038/nature21697 (2017).