Soluble delta-like 1 homolog decreases in patients with acromegaly following pituitary surgery: A potential mediator of adipogenesis suppression by growth hormone?

Abstract

OBJECTIVE GH excess in acromegaly leads to lower fat mass and insulin resistance; both reverse following pituitary surgery. Soluble delta like-1 homolog (sDlk1) inhibits adipocyte differentiation and may mediate the antiadipogenic effects of GH. It is released into the circulation by ectodomain shedding through 'A Disintegrin And Metalloproteinase domain 17' (ADAM17), which also sheds soluble α-Klotho (sKlotho). Klotho is a transmembrane protein, which influences life span. sKlotho inhibits insulin signalling, and is markedly elevated in acromegaly and decreases after surgery. Therefore, we examined if sDlk1 parallels the course of sKlotho, which could explain the well-known changes in fat mass in patients with acromegaly after surgery. DESIGN We measured serum levels of GH, IGF-1, sDlk1 and sKlotho (both by ELISA) in 42 treatment-naïve acromegaly patients (20 females/22 males) before and 1-3 months after transsphenoidal surgery. Data are presented as median(interquartile range). RESULTS GH decreased in all patients postoperatively (in 32/42 to <1 ng/ml during oral glucose tolerance testing). Likewise, IGF-1 and sKlotho decreased in all patients, from 587 (432-708) to 195 (133-270) ng/ml, and from 4.0 (2.7-5.9) to 0.7 (0.6-1.2) ng/ml, respectively; sDlk1 fell in 40/42 subjects, from 10.7 (5.8-13.4) to 7.1 (3.7-10.4) ng/ml following pituitary surgery. P < 0.0001 for all parameters. CONCLUSIONS sDlk1 declined after pituitary surgery in our patients with acromegaly, but to a lesser extent than sKlotho. It remains to be seen whether this may contribute to the well-known postoperative changes in body composition. Our findings may extend beyond the scope of acromegaly, and thus further elucidate mechanisms in the fields of obesity and anti-ageing.