Hormone Produced by Bone Cells Could Treat Obesity
A hormone that can suppress food intake in mice is showing similar results in humans and non-human primates, according to a new study published in eLife.
The hormone, called lipocalin-2 (LCN2), is mainly produced by bone cells and could be used as a potential treatment for obesity.
“Previous studies have shown that giving LCN2 to mice long-term reduces food intake and prevents weight gain, without leading to a slowdown in metabolism,” says lead author Peristera-Ioanna Petropoulou, PhD, who was a postdoctoral research scientist at Columbia University Vagelos College of Physicians and Surgeons at the time of the study. “We wanted to see whether LCN2 has similar effects in humans and whether a dose of it would be able to cross the blood-brain barrier.”
LCN2 increases after meals, reduces food intake
The team analyzed data from four different studies of people who were given a meal after an overnight fast. The researchers found that, on average, LCN2 levels increased after the meal, which coincided with how satisfied the participants felt after eating. However, in people who were overweight or had obesity, LCN2 levels decreased after a meal. People who had lost weight after gastric bypass surgery were found to have a restored sensitivity to LCN2.
Next the team explored whether treatment with the hormone might reduce food intake and prevent weight gain in non-human primates. After treatment with LCN2 for a week, the monkeys ate 21% less than their counterparts who were treated only with saline. Measurements showed a decline in body weight, body fat, and blood fat levels in treated animals.
LCN2 binds to brain's hypothalamus
MRI and PET scans of the non-human primates (shown above) revealed that LCN2 crosses from blood into the brain and binds to the hypothalamus to suppress food intake.
“This study suggests that loss of post-meal LCN2 regulation is a new mechanism that contributes to obesity,” says senior author Stavroula Kousteni, PhD, professor of physiology & cellular biophysics at Columbia University Vagelos College of Physicians and Surgeons.
“Restoring LCN-2 function could be used as a potential treatment for weight-loss.”
This article was adapted from a press release by eLife.
The research paper is titled “Lipocalin-2 is an anorexigenic signal in primates.”
Other contributors from Columbia University Vagelos College of Physicians and Surgeons: Ioanna Mosialou, Steven Shikhel, Lihong Hao, Konstantinos Panitsas, Brygida Bisikirska, Na Luo, Fabiana Bahna, Jongho Kim, Patrick Carberry, Francesca Zanderigo, Norman Simpson, Mihran Bakalian, Suham Kassir, Lawrence Shapiro, Mark D. Underwood, Sue Shapses, Blandine Laferrère, Akiva Mintz, J. John Mann, and Mishaela Rubin.
Additional contributors: Christina M. May (Wake Forest School of Medicine), Kiran Kumar Solingapuram Sai (Wake Forest School of Medicine), Matthew J. Jorgensen (Wake Forest School of Medicine), and Cyrille B. Confavreux (Université de Lyon).
The study was supported by grants from the National Institutes of Health (UL1TR001873, T32HL120826, P01AG032959, R01 DK067561, P30 DK26687-30, P30 DK063608, UL1 TR000040).
The authors declare no financial or other conflicts of interest.