Longevity & AgingBlocking a sclerostin-fat cell interaction may restore lipid and glucose balance in mice
Sclerostin, a bone-building inhibitor, also impairs fat and sugar metabolism. Researchers found serum sclerostin was higher in people newly diagnosed with type 2 diabetes and in postmenopausal osteoporosis patients with diabetes. In mice, truncating or mutating sclerostin's loop3 region, or blocking it with a loop3-specific aptamer (Apc001OA), shrank fat pads and adipocytes, lowered free fatty acids, and improved glucose tolerance and insulin sensitivity, while also improving bone structure and strength. The paper's title and abstract point to LRP4 on fat cells as the loop3 receptor, and blocking that interaction reduced sclerostin's metabolic harm in vitro and in vivo. The approach could offer a way to treat osteoporosis and diabetes together without the cardiovascular warnings attached to current sclerostin antibodies, but the evidence so far is preclinical and the human data are correlational.
