Release date: 2018-01-19
The Klotho protein, named after the goddess of fate in Greek mythology, plays an important role in regulating longevity and metabolism. Recently, a study at Yale University revealed the three-dimensional structure of a protein in the Klotho family, β-Klotho, and elucidated its complex mechanisms and therapeutic potential.
Researchers say the findings, published in Nature, may have implications for a variety of diseases, including diabetes, obesity, and certain cancers.
The transmembrane protein Klotho family is located on the cell surface of specific tissues. These proteins bind to a range of hormones, the designated fibroblast growth factor FGFs, which act in an endocrine manner and regulate key metabolic processes in organs such as the liver, kidneys and brain.
To understand how β-Klotho works, the team used X-ray crystallography to see high-resolution 3D views of these proteins.
The researchers found that FGF21 is an endocrine factor synthesized by the liver that promotes the uptake of glucose by fat cells. The activity of FGF21 is dependent on β-Klotho, and when combined, FGF21 stimulates insulin sensitivity and glucose metabolism, resulting in weight loss.
The researchers said that a new understanding of β-Klotho and FGF21 can guide the treatment of diseases such as type 2 diabetes in obese patients.
Joseph Schlessinger, senior author and senior author of pharmacology at Yale University School of Medicine, said, "Like insulin, FGF21 stimulates metabolism, including glucose uptake. In some clinical trials of animals and FGF21, it can be used without changing food intake. In the case of increased calorie consumption, we now understand how to increase the biological activity of FGF21."
Schlessinger also introduced a new variant of FGF21, which is 10 times more potent and cellular than FGF21.
In addition, the team also demonstrated how structurally related saccharolytic enzymes (glycosidases) degrade sugar molecules, thereby reducing blood sugar lowering. In Schlessinger's view, this may not be a coincidence.
Schlessinger and colleagues have unlocked the structure of beta-Klotho and hope to target diabetes and obesity by developing drugs that enhance this pathway. Instead, they hope to use drugs that block the route to explore drugs that treat diseases such as liver cancer and bone disease.
Schlessinger said that the next step is to develop new and powerful blockers and conduct animal experiments.
Reference material
Secrets of longevity protein revealed in new study
Source: Bio-Exploration
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