Written by: Lily Song

     Obesity is a disease involving an excessive amount of body fat. It affects both adults and children and is correlated to more than half of the top ten leading causes of death in the US. Worldwide, it has nearly tripled between 1975 and 2016. People with obesity have a greater likelihood of developing many health diseases, such as type 2 diabetes, cardiovascular disease, chronic kidney disease, high blood pressure, stroke, depression, and certain cancers (Mayo Clinic, 2020). Unfortunately, due to the limited understanding of energy homeostasis, the mechanism that sustains weight by observing energy intake to energy expenditure obesity is a problem that challenges researchers. There are ways to tackle obesity, including changes in diet and increased exercise; but, these methods can be difficult to sustain (Mayo Clinic, 2020). Additionally, individuals can turn to prescription medications and weight-loss medical procedures for treating obesity, but these have side effects that could prevent long-term practice (World Health Organization, 2020). Overall, due to our limited knowledge about obesity and its epidemic proportions across the world, the need for an efficient obesity treatment with long term benefits and minimal side effects is prevalent. 

Lipocalin-2 

     A recent study published in the journal eLife presents a promising opportunity to treat obesity through the regulation of a hormone called Lipocalin-2 (LCN2). Lipocalin-2 is a hormone found in mice and humans that is mainly produced by bone cells (Guo et al., 2020). Previous studies with lean and obese mice have shown that LCN2 effectively suppresses appetite and body-weight gain by acting on the hypothalamus, the brain center regulating appetite and energy balance, within the brain. Oftentimes, humans who tackle obesity by decreasing food intake suffer from metabolic stagnation. This phenomenon occurs because when one consumes significantly less food, their brain slows down metabolism to keep the body functioning on fewer calories. However, LCN2 overcomes this compensatory decrease in energy expenditure, making it a major asset to efficient weight-loss (Petropoulou et al., 2020). LCN2’s ability to cause a loss of appetite relies largely on its ability to cross the blood-brain barrier (BBB) and activate the melanocortin four receptor (MC4R)-dependent pathway, which is currently known as one of the most potent regulators of obesity (Guo et al., 2020). But, whether this hormone has the same effects in humans and whether it has the ability to cross the human blood-brain barrier is still being investigated. 

Figure 1

A 3D image of LCN2

Source: Wikipedia.org

Promising Results 

     Now, studies show that LCN2 was successful in suppressing appetite in humans and monkeys. In studies involving humans, LCN2 levels increased after a meal in individuals with normal weight or overweight, but not in individuals with obesity. Higher levels of LCN2 in a person’s blood were also correlated with a feeling of reduced hunger. After giving monkeys LCN2 for a week, they observed a 28% decrease in food intake and also ate 21% less than the control group, who was treated with just saline. After the treatment period, measurements of body weight, body fat and blood fat levels in the animals who were treated with LCN2 showed a declining trend. Brain scans displayed that the LCN2 was able to cross the blood-brain barrier in monkeys and bind to the hypothalamus, suggesting successful suppressed food intake in non-human primates. Furthermore, there were no toxic effects on the treated animals in short-term studies. 

Conclusion

     Overall, obesity is an issue that must be tackled worldwide. In the US alone, over 40% of adults suffer from the disease, and its consequences go beyond mere cosmetic concerns. There are several complications involved with it, including heart disease and strokes, and it can also diminish one’s overall quality of life. Thankfully, the results of the studies discussed show that the LCN2 hormone is a promising basis for future clinical use in the next level of battling obesity. Not only is it able to suppress hunger and cross the human blood-brain barrier, it also has little to none harmful side effects. Researchers are hopeful for this emerging novel finding. 

References and Sources

eLife. (2020, November 24). Hormone found to switch off hunger could help tackle obesity: New findings suggest a hormone called Lipocalin-2 could be used as a potential treatment for obesity. ScienceDaily. Retrieved December 22, 2020 from www.sciencedaily.com/releases/2020/11/201124122921.htm

Guo, H., Bazuine, M., Jin, D., Huang, M. M., Cushman, S. W., & Chen, X. (2013). Evidence for the regulatory role of lipocalin 2 in high-fat diet-induced adipose tissue remodeling in male mice. Endocrinology, 154(10), 3525–3538. https://doi.org/10.1210/en.2013-1289 

Obesity and Overweight. (2020, April 1). Retrieved December 23, 2020, from https://www.who.int/news-room/fact-sheets/detail/obesity-and-overweight 

Obesity. (2020, November 18). Retrieved December 23, 2020, from https://www.mayoclinic.org/diseases-conditions/obesity/symptoms-causes/syc-20375742

Petropoulou, P., Mosialou, I., Shikhel, S., Hao, L., Panitsas, K., Bisikirska, B., Luo, N., Bahna, F., Kim, J., Carberry, P., Zanderigo, F., Simpson, N., Bakalian, M., Kassir, S., Shapiro, L., Underwood, M., May, C., Sai, K., Jorgensen, M., Confavreux, C., Shapses, S., Laferrère, B., Mintz, A., Mann, J., Rubin, M., & Kousteni, S. (2020). Lipocalin-2 is an anorexigenic signal in primates. eLife, 2020; 9 DOI: 10.7554/eLife.58949