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If you have any medical questions or concerns, please talk to your healthcare provider. The articles on Health Guide are underpinned by peer-reviewed research and information drawn from medical societies and governmental agencies. However, they are not a substitute for professional medical advice, diagnosis, or treatment.
Why is it that two people can eat the same thing and respond differently? One person may feel full while the other is still hungry. Another might burn off calories quickly while the other doesn’t.
It turns out there is more to appetite and weight than just what you eat and how much you exercise. Hormones like leptin are one important part of the process, too.
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What is leptin?
Leptin is a hormone that helps regulate appetite, metabolism, parts of the immune system, and more. It’s produced in the body by a type of fat tissue called white adipose tissue.
Sometimes leptin is called a fullness hormone. That’s because it helps control how many calories you take in and how many you burn (otherwise known as your energy balance) (Dornbush, 2021).
How does leptin work in the body?
After you’ve consumed enough calories during a meal, your fat cells release leptin. Leptin binds to a leptin receptor protein, which sends signals that you’re full to the brain or central nervous system. This feeling of fullness (satiety) signals you to stop eating and burn off more calories.
Your body uses fat cells called adipocytes as fuel, and when you’re well-fed, leptin signals your body to burn off this fuel. During periods of starvation, you don’t have enough calories or body fat stored up. This makes your levels of leptin drop, signaling your body to eat more and store calories for energy instead of burning them off (Dornbush, 2021).
Leptin and ghrelin
The hormone leptin doesn’t regulate appetite all by itself. It works hand in hand with another hormone called ghrelin. Ghrelin is an appetite hormone that tells you when to eat and store calories. Your appetite and weight are strongly influenced by the balance between leptin and ghrelin.
For example, leptin levels decrease to save calories during starvation while ghrelin levels increase. This indicates that you’re hungry and need to eat more. When you’re well-fed, the reverse happens (Klok, 2007).
Set point theory: what is it, and does it affect your weight?
Does leptin affect weight?
It can. Eating triggers fat cells to release leptin, which leaves you feeling full and encourages your metabolism to burn more calories. This complex and fascinating system is set up to prevent overeating and excess weight gain (Dalamaga, 2013).
Leptin is made in adipose or fat tissue. The more adipose you have, the more leptin you make (Park, 2015). You would think that producing more leptin means losing more weight, but that’s not necessarily the case.
What is leptin resistance?
Leptin resistance occurs when the brain can’t receive or respond to the signals leptin sends out. Fat tissue still accumulates and produces leptin with leptin resistance––the catch is your brain doesn’t register that you’re full.
Since you still feel hungry, you continue eating and building fat tissue. Your body doesn’t respond to leptin signals to burn off calories, so you’re basically eating more without burning anything off, which can result in weight gain (Myers, 2012).
Leptin resistance may be congenital (meaning you’re born with it) or be caused by inflammation in a part of the brain called the hypothalamus (Thaler, 2012).
How does ashwagandha help with weight loss?
Leptin for obesity treatment
Since leptin makes you feel full and burns calories, it seems logical that you could use it to treat obesity. However, studies have shown that giving people leptin doesn’t help (Paz-Filho, 2011).
This is because people with obesity already produce leptin. In fact, since they have more fat tissue, they usually have higher than average leptin levels, so adding more isn’t helpful (Maffei, 1995).
There’s one exception to this. Some individuals have congenital leptin deficiency (CLD), meaning they were born with almost no leptin at all (Sáinz, 2015). People with CLD may have obesity and are at risk for complications like high cholesterol, cardiovascular disease, and type 2 diabetes.
People with CLD are sensitive to the effects of leptin but don’t have enough of the hormone. When they’re treated with leptin, it basically replaces a missing part. In this circumstance, leptin treatment helps reduce weight, lower cholesterol, and balance blood sugar (Paz-Filho, 2011).
Leptin deficiency is much less common than leptin resistance, so this treatment isn’t helpful for everyone (Vatier, 2012).
Should I take leptin supplements?
Ironically, leptin supplements aren’t actually leptin. Also called leptin resistance pills, these supplements contain ingredients like vitamins and extracts that claim to increase leptin sensitivity in people who are resistant (Sáinz, 2015).
There’s evidence that some of the ingredients (like linoleic acid and green tea) slightly affect leptin levels, but there’s no proof these help with appetite, weight loss, or leptin resistance (Medina, 2000; Haghighatdoost, 2018).
Types of food proven to help with losing weight
So if you’re taking leptin supplements to help with appetite or weight loss, you might not see the results you’re after. In the meantime, here are some steps you can take to improve leptin resistance:
- Cut down on fats and carbs. A diet that’s higher in fats and processed carbohydrates increases inflammation in the body. More inflammation can lead to leptin resistance (De Souza, 2005; Ghanim, 2009).
- Eat more protein. When you have this condition, getting rid of excess leptin may improve sensitivity to it (Zhao, 2019). Studies have found that participants who ate a high-protein diet saw decreased leptin levels and increased feelings of fullness (Weigle, 2005).
- Get enough sleep. When you’re busy, it’s tempting to skip sleep in order to get more things done. But not getting enough sleep can affect leptin levels, which impacts your metabolism and can cause weight gain (Spiegel, 2004).
- Exercise. One of the many benefits of regular exercise is that it can significantly lower excess leptin circulating in your system (Reseland, 2001).
- Reduce stress. Leptin levels are also closely tied to your emotional state (Licinio, 2015). Keeping stress in check and taking care of your mental health can help keep hormone levels balanced.
Morbid obesity: risk factors, diagnosis, and treatment
Leptin is an important hormone for appetite and weight regulation, but leptin supplements aren’t a helpful obesity treatment. A healthcare provider can help you determine whether you may be leptin resistant and find ways to improve your sensitivity.
- Allison, M. B. & Myers, M. G., Jr. (2014). 20 years of leptin: connecting leptin signaling to biological function. The Journal of Endocrinology, 223(1), 25–35. doi:10.1530/JOE-14-0404. Retrieved from https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4170570/
- Considine, R. V., Sinha, M. K., Heiman, M. L., et al. (1996). Serum immunoreactive-leptin concentrations in normal-weight and obese humans. The New England Journal of Medicine, 334(5), 292–295. doi:10.1056/NEJM199602013340503. Retrieved from https://www.nejm.org/doi/10.1056/NEJM199602013340503?url_ver=Z39.88-2003&rfr_id=ori:rid:crossref.org&rfr_dat=cr_pub%20%200www.ncbi.nlm.nih.gov
- Dalamaga, M., Chou, S. H., Shields, K., et al. (2013). Leptin at the intersection of neuroendocrinology and metabolism: current evidence and therapeutic perspectives. Cell Metabolism, 18(1), 29–42. doi:10.1016/j.cmet.2013.05.010. Retrieved from https://www.sciencedirect.com/science/article/pii/S1550413113002003
- De Souza, C. T., Araujo, E. P., Bordin, S., et al. (2005). Consumption of a fat-rich diet activates a proinflammatory response and induces insulin resistance in the hypothalamus. Endocrinology, 146(10), 4192–4199. doi:10.1210/en.2004-1520. Retrieved from https://pubmed.ncbi.nlm.nih.gov/16002529/
- Dornbush, S. & Aeddula, N. R. (2021). Physiology, Leptin. StatPearls. Retrieved from https://www.ncbi.nlm.nih.gov/books/NBK537038/
- Elmquist, J. K., Coppari, R., Balthasar, N., et al. (2005). Identifying hypothalamic pathways controlling food intake, body weight, and glucose homeostasis. The Journal of Comparative Neurology, 493(1), 63–71. doi:10.1002/cne.20786. Retrieved from https://pubmed.ncbi.nlm.nih.gov/16254991/
- Friedman, J. (2014). 20 years of leptin: leptin at 20: an overview. The Journal of Endocrinology, 223(1), 1–8. doi:10.1530/JOE-14-0405. Retrieved from https://pubmed.ncbi.nlm.nih.gov/25121999/
- Ghanim, H., Abuaysheh, S., Sia, C. L., et al. (2009). Increase in plasma endotoxin concentrations and the expression of Toll-like receptors and suppressor of cytokine signaling-3 in mononuclear cells after a high-fat, high-carbohydrate meal: implications for insulin resistance. Diabetes Care, 32(12), 2281–2287. doi:10.2337/dc09-0979. Retrieved from https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2782991/
- Haghighatdoost, F., Nobakht M Gh, B. F., & Hariri, M. (2018). Effect of green tea on plasma leptin and ghrelin levels: A systematic review and meta-analysis of randomized controlled clinical trials. Nutrition, 45, 17–23. doi:10.1016/j.nut.2017.06.022. Retrieved from https://pubmed.ncbi.nlm.nih.gov/29129232/
- Jakobsdottir, S., van Nieuwpoort, I. C., van Bunderen, C. C., et al. (2016). Acute and short-term effects of caloric restriction on metabolic profile and brain activation in obese, postmenopausal women. International Journal of Obesity, 40(11), 1671–1678. doi:10.1038/ijo.2016.103. Retrieved from https://pubmed.ncbi.nlm.nih.gov/27216819/
- Kleinridders, A., Schenten, D., Könner, A. C., et al. (2009). MyD88 signaling in the CNS is required for development of fatty acid-induced leptin resistance and diet-induced obesity. Cell Metabolism, 10(4), 249–259. doi:10.1016/j.cmet.2009.08.013. Retrieved from https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3898351/
- Klok, M. D., Jakobsdottir, S., & Drent, M. L. (2007). The role of leptin and ghrelin in the regulation of food intake and body weight in humans: a review. Obesity Reviews, 8(1), 21–34. doi:10.1111/j.1467-789X.2006.00270.x. Retrieved from https://pubmed.ncbi.nlm.nih.gov/17212793/
- Leidy, H. J. (2014). Increased dietary protein as a dietary strategy to prevent and/or treat obesity. Missouri Medicine, 111(1), 54–58. Retrieved from https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6179508/
- Licinio, J., Negrao, A. B., & Wong, M. L. (2014). Plasma leptin concentrations are highly correlated to emotional states throughout the day. Translational Psychiatry, 4(10), e475. doi:10.1038/tp.2014.115. Retrieved from https://www.nature.com/articles/tp2014115
- Maffei, M., Halaas, J., Ravussin, E., et al. (1995). Leptin levels in human and rodent: measurement of plasma leptin and ob RNA in obese and weight-reduced subjects. Nature Medicine, 1(11), 1155–1161. doi:10.1038/nm1195-1155. Retrieved from https://pubmed.ncbi.nlm.nih.gov/7584987/
- Medina, E. A., Horn, W. F., Keim, N. L., et al. (2000). Conjugated linoleic acid supplementation in humans: effects on circulating leptin concentrations and appetite. Lipids, 35(7), 783–788. doi:10.1007/s11745-000-0586-y. Retrieved from https://pubmed.ncbi.nlm.nih.gov/10941880/
- Montague, C. T., Farooqi, I. S., Whitehead, J. P., et al. (1997). Congenital leptin deficiency is associated with severe early-onset obesity in humans. Nature, 387(6636), 903–908. doi:10.1038/43185. Retrieved from https://www.nature.com/articles/43185
- Myers, M. G., Jr, Heymsfield, S. B., Haft, C., et al. (2012). Challenges and opportunities of defining clinical leptin resistance. Cell Metabolism, 15(2), 150–156. doi:10.1016/j.cmet.2012.01.002. Retrieved from https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3281561/
- Park, H. K. & Ahima, R. S. (2015). Physiology of leptin: energy homeostasis, neuroendocrine function and metabolism. Metabolism, 64(1), 24–34. doi:10.1016/j.metabol.2014.08.004. Retrieved from https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4267898/
- Paz-Filho, G., Wong, M. L., & Licinio, J. (2011). Ten years of leptin replacement therapy. Obesity Reviews, 12(5), e315–e323. doi:10.1111/j.1467-789X.2010.00840.x. Retrieved from https://pubmed.ncbi.nlm.nih.gov/21410864/
- Reseland, J. E., Anderssen, S. A., Solvoll, K., et al. (2001). Effect of long-term changes in diet and exercise on plasma leptin concentrations. The American Journal of Clinical Nutrition, 73(2), 240–245. doi:10.1093/ajcn/73.2.240. Retrieved from https://pubmed.ncbi.nlm.nih.gov/11157319/
- Sáinz, N., González-Navarro, C. J., Martínez, J. A., & Moreno-Aliaga, M. J. (2015). Leptin signaling as a therapeutic target of obesity. Expert Opinion on Therapeutic Targets, 19(7), 893–909. doi:10.1517/14728222.2015.1018824. Retrieved from https://pubmed.ncbi.nlm.nih.gov/25726860/
- Spiegel, K., Leproult, R., L’hermite-Balériaux, M., et al. (2004). Leptin levels are dependent on sleep duration: relationships with sympathovagal balance, carbohydrate regulation, cortisol, and thyrotropin. The Journal of Clinical Endocrinology and Metabolism, 89(11), 5762–5771. doi:10.1210/jc.2004-1003. Retrieved from https://pubmed.ncbi.nlm.nih.gov/15531540/
- Thaler, J. P., Yi, C. X., Schur, E. A., et al. (2012). Obesity is associated with hypothalamic injury in rodents and humans. The Journal of Clinical Investigation, 122(1), 153–162. doi:10.1172/JCI59660. Retrieved from https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3248304/
- Vatier, C., Gautier, J. F., & Vigouroux, C. (2012). Therapeutic use of recombinant methionyl human leptin. Biochimie, 94(10), 2116–2125. doi:10.1016/j.biochi.2012.03.013. Retrieved from https://pubmed.ncbi.nlm.nih.gov/22464954/
- Weigle, D. S., Breen, P. A., Matthys, C. C., et al. (2005). A high-protein diet induces sustained reductions in appetite, ad libitum caloric intake, and body weight despite compensatory changes in diurnal plasma leptin and ghrelin concentrations. The American Journal of Clinical Nutrition, 82(1), 41–48. doi:10.1093/ajcn.82.1.41. Retrieved from https://pubmed.ncbi.nlm.nih.gov/16002798/
- Zarouna, S., Wozniak, G., & Papachristou, A. I. (2015). Mood disorders: A potential link between ghrelin and leptin on human body? World Journal of Experimental Medicine, 5(2), 103–109. doi:10.5493/wjem.v5.i2.103. Retrieved from https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4436933/
- Zhao, S., Kusminski, C. M., Elmquist, J. K., & Scherer, P. E. (2020). Leptin: Less Is More. Diabetes, 69(5), 823–829. doi:10.2337/dbi19-0018. Retrieved from https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7171955/
- Zhao, S., Zhu, Y., Schultz, R. D., et al. (2019). Partial Leptin Reduction as an Insulin Sensitization and Weight Loss Strategy. Cell Metabolism, 30(4), 706–719. doi:10.1016/j.cmet.2019.08.005. Retrieved from https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6774814/