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.

中文翻译：

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垂体手术后肢端肥大症患者的可溶性delta-like 1同源物减少：生长激素抑制脂肪生成的潜在介质？

目的

肢端肥大症中的GH过量会降低脂肪量和胰岛素抵抗；垂体手术后两者均逆转。可溶性delta like-1同源物（sDlk1）抑制脂肪细胞分化，并可能介导GH的抗脂肪形成作用。它通过“ A整联蛋白和金属蛋白酶结构域17”（ADAM17）的胞外域脱落释放到循环系统中，后者也释放出可溶性α-Klotho（sKlotho）。Klotho是一种跨膜蛋白，会影响寿命。sKlotho抑制胰岛素信号传导，肢端肥大症明显升高，术后降低。因此，我们检查了sDlk1是否与sKlotho的过程平行，这可以解释众所周知的肢端肥大症患者术后脂肪量的变化。

设计

我们测量了经蝶窦手术之前和之后1至3个月的42例初治肢端肥大症患者（20位女性/ 22位男性）的GH，IGF-1，sDlk1和sKlotho（均通过ELISA）的血清水平。数据以中位数（四分位间距）表示。

结果

术后所有患者的GH均下降（口服葡萄糖耐量试验期间GH从32/42降至<1 ng / ml）。同样，所有患者的IGF-1和sKlotho均从587（432-708）降至195（133-270）ng / ml，从4.0（2.7-5.9）降至0.7（0.6-1.2）ng / ml。 ; sDlk1在40/42名受试者中下降，从垂体手术后的10.7（5.8-13.4）降至7.1（3.7-10.4）ng / ml。对于所有参数，P <0.0001。

结论

垂体手术后，肢端肥大症患者的sDlk1下降，但程度比sKlotho小。这是否可能导致众所周知的术后身体成分改变尚待观察。我们的发现可能超出肢端肥大症的范围，因此进一步阐明了肥胖和抗衰老领域的机制。