Klotho proteins bind to a family of hormones, designated endocrine FGFs, that regulate critical metabolic processes.

‘Beta-Klotho binds to a hormone FGF21 that stimulates insulin sensitivity and glucose metabolism, causing weight loss.’

The study findings, could have implications for therapies developed to treat a wide range of medical conditions, including diabetes, obesity, and certain cancers, the research team said. 




The Klotho family of two receptor proteins are located on the surface of cells of specific tissues. The proteins bind to a family of hormones, designated endocrine FGFs, that regulate critical metabolic processes in the liver, kidneys, and brain, among other organs. To understand how beta-Klotho works, the research team used X-ray crystallography, a technique that provides high-resolution, three-dimensional views of these proteins.
Striking Features of The Protein
- First, beta-Klotho is the primary receptor that binds to FGF21, a key hormone produced upon starvation.
- When bound to beta-Klotho, FGF21 stimulates insulin sensitivity and glucose metabolism, causing weight loss.
- This new understanding of beta-Klotho and FGF21 can guide the development of therapies for conditions such as type 2 diabetes in obese patients, the researchers said.
Additionally, the research team presented evidence of how a structurally-related enzyme, glycosidase, which breaks down sugars, evolved into a receptor for a hormone that lowers blood sugar -- which may not be a coincidence, Schlessinger added.
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"The next step will be to make better hormones, make new potent blockers, do animal studies, and move forward," Schlessinger said.