Menu

Hormone Released by Bone Suppresses Appetite

A protein secreted by osteoblasts crosses the blood-brain barrier to regulate hunger in mice.

Mar 8, 2017
Abby Olena

Slice of a mouse hypothalamusWIKIMEDIA, ZABBNResearchers have shown that a hormone secreted by bone, called lipocalin 2 (LCN2), suppresses appetite in mice. The results, published today (March 8) in Nature, suggest that LCN2 crosses the rodents’ blood-brain barrier and binds a receptor in the hypothalamus. The team also found a link between body weight and LCN2 levels in people with type 2 diabetes.

The authors “have identified a protein that’s secreted from bone that has a pretty significant impact on feeding behavior,” Lora Heisler of the University of Aberdeen in Scotland, who did not participate in the work, told The Scientist. “And the fact that they found that some supporting evidence in humans is really exciting.”

“We have found a new role for bone as an endocrine organ, and that is its ability to regulate appetite,” said study coauthor Stavroula Kousteni of Columbia University in New York City.

Scientists had previously identified LCN2 as a protein expressed in fat cells, but Kousteni and colleagues showed that it is enriched 10-fold in osteoblasts. When they generated mice without LCN2 in their osteoblasts, levels of the circulating hormone dropped 67 percent. These mice ate more than control animals and showed increases in fat mass and body weight.

When the authors injected LCN2 into wild-type or obese mice, the rodents ate less food. The treated animals showed decreases in body weight, fat mass, and weight gain. LCN2 injections also led to increases in insulin levels and glucose tolerance, the scientists showed.

The team then injected the hormone intraperitoneally into LCN2-knockout mice, which restored normal serum levels of the peptide. LCN2 accumulated in the animals’ brains, especially their hypothalamuses, suggesting that the hormone can cross the blood-brain barrier. LCN2 injections directly into the brains of knockout mice suppressed appetite and decreased weight gain.

Kousteni and colleagues next investigated the interaction of LCN2 with the melanocortin 4 receptor (MC4R), which is expressed in the hypothalamus and is known to be involved in appetite regulation. Injection of LCN2 activated cells in the hypothalamus that express MC4R in wild-type mice, but not in MC4R-knockout mice, they found. And upon injection of LCN2, MC4R-knockout mice did not experience the same decreases in appetite or body weight, or increases in insulin sensitivity or glucose tolerance, as their wild-type counterparts. The team’s findings suggest that LCN2 binds to and activates MC4R.

In people with type 2 diabetes, the researchers reported, body weight was inversely linked to serum levels of LCN2. The team also found that some patients with MC4R mutations have higher levels of circulating LCN2. This was unsurprising, as ligands are often expressed at higher levels when their receptors are inactivated.

“This [study] is still very initial, but I think this is important and the effects they have are quite strong,” said Marcelo Dietrich of Yale University School of Medicine in Newhaven, Connecticut, who did not participate in the work. Dietrich highlighted several open questions, including the role skeletal movement may play in LCN2 regulation and why a bone-secreted protein appears to regulate appetite.

“The big question that still remains unexplored at this point [is]: Why would something that’s secreted by the bone suppress food intake?” echoed Michael Krashes of the National Institute of Diabetes and Digestive and Kidney Diseases in Bethesda, Maryland, who did not participate in the study. “The next step is to try and figure out why that is,” he added.

Future work could also take a more translational direction. The team plans to investigate whether LCN2 functions in humans and non-human primates as it does in mice. And Kousteni said she is optimistic about the potential of LCN2 as a treatment for obesity. “We are hopeful about the lack of any toxic effects because it’s a naturally occurring protein,” she said. “We see that if we give it in doses as high as 3,000-fold higher than the circulating [level], nothing happens to the mice. They’re still fine.”

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

February 2019

Big Storms Brewing

Can forests weather more major hurricanes?

Marketplace

Sponsored Product Updates

Bio-Rad Showcases New Automation Features of its ZE5 Cell Analyzer at SLAS 2019
Bio-Rad Showcases New Automation Features of its ZE5 Cell Analyzer at SLAS 2019
Bio-Rad Laboratories, Inc. (NYSE: BIO and BIOb) today showcases new automation features of its ZE5 Cell Analyzer during the Society for Laboratory Automation and Screening 2019 International Conference and Exhibition (SLAS) in Washington, D.C., February 2–6. These capabilities enable the ZE5 to be used for high-throughput flow cytometry in biomarker discovery and phenotypic screening.
Andrew Alliance and Sartorius Collaborate to Provide Software-Connected Pipettes for Life Science Research
Andrew Alliance and Sartorius Collaborate to Provide Software-Connected Pipettes for Life Science Research
Researchers to benefit from an innovative software-connected pipetting system, bringing improved reproducibility and traceability of experiments to life-science laboratories.
Corning Life Sciences to Feature 3D Cell Culture Technologies at SLAS 2019
Corning Life Sciences to Feature 3D Cell Culture Technologies at SLAS 2019
Corning Incorporated (NYSE: GLW) will showcase advanced 3D cell culture technologies and workflow solutions for spheroids, organoids, tissue models, and applications including ADME/toxicology at the Society for Laboratory Automation and Screening (SLAS) conference, Feb. 2-6 in Washington, D.C.
Corning Introduces New 1536-well Spheroid Microplate
Corning Introduces New 1536-well Spheroid Microplate
High-throughput spheroid microplate benefits cancer research, drug screening