Posted on Dec 09, 2020, 7 a.m.
Researchers have found that the hormone called LCN2 suppressed hunger after eating and that levels were depressed in those with obesity; giving this hormone to monkeys reduced appetite without causing side effects in a proof of concept study.
Excess weight is increasingly common in the United States. More than 40% of adults are now considered obese. Obesity increases the risk for a variety of health problems, including heart disease, type 2 diabetes, and certain types of cancer.
Unfortunately, extra weight can be difficult to lose and keep off. Changes in diet and exercise can help some people lose weight. However, weight loss can trigger the body to slow its metabolism, causing a quick rebound in weight gain.
Several drugs have been approved to help with weight loss, but some have unpleasant side effects, and none have been shown to contribute to a sustained reduction in weight. Better treatments to help people with obesity lose weight are needed.
Studies in mice have shown that a hormone released from the bone called lipocalin-2 (LCN2) helps signal to the brain that the stomach is full and suppress excess food intake.
Researchers led by Dr. Stavroula Kousteni at Columbia University examined whether LCN2 also plays a role in regulating appetite in humans and monkeys. The research was funded in part by several NIH components. Results were published on November 24, 2020, in eLife.
The team first tracked blood levels of LCN2 after a meal in lean women and in both women and men who were either overweight or obese.
LCN2 levels increased after eating in people of normal weight. However, they didn’t consistently rise in those who were overweight or obese, and even decreased in some. In people with severe obesity, LCN2 levels consistently fell after meals. However, after gastric bypass surgery, levels of the hormone rose after meals, suggesting that the surgery restored their normal LCN2 response.
Levels of LCN2 also correlated with perceptions of hunger after eating. People with more LCN2 in their blood reported feeling fuller after a meal.
The researchers next used imaging to track LCN2 in monkeys. After being infused into a vein, the hormone traveled into the brain and bound to receptors in the hypothalamus. The hypothalamus is the brain area that regulates appetite and energy balance. LCN2 also bound to hypothalamus tissue samples taken from both primate and human brains.
To test the potential of LCN2 as an appetite suppressant, the team gave the hormone to healthy, lean monkeys for a week. During treatment, the monkeys ate almost 30% less than they did without added LCN2, and 20% less than they did when given a placebo. No toxic effects were detected.
“Our results show that the hormone can curb appetite with negligible toxicity and lay the groundwork for the next level of LCN2 testing for clinical use,” Kousteni says.
More studies will be needed to better understand how LCN2 works in the body and brain, and to determine safe doses for potential testing in human trials.
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Lipocalin-2 is an anorexigenic signal in primates. Petropoulou PI, 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 MD, May CM, Soligapuram Sai KK, Jorgensen MJ, Confavreux CB, Shapses S, Laferrère B, Mintz A, Mann JJ, Rubin M, Kousteni S. Elife. 2020 Nov 24;9:e58949. doi: 10.7554/eLife.58949. PMID: 33231171.