(1) Patients controlled by somatostatin analog fail to suppress growth hormone in response to both mixed meals and oral glucose tolerance test (2) This phenomenon is likely to result in elevated serum growth hormone levels during everyday life in somatostatin analog-treated patients, (3) We postulate that measuring growth hormone levels during oral glucose tolerance test is useful to unmask potential somatostatin analog under-treatment in the presence of 'safe' insulin-like growth factor-I levels.
Adipose tissue is the primary energy reservoir of the human body, which also possesses endocrine functions. The glucagon‐like peptide agonist liraglutide produces weight loss, although the specific effects on adipose tissue are unknown. We aimed to characterize the white adipose tissue composition and pericellular fibrosis of subcutaneous adipose tissue in response to liraglutide treatment. Furthermore, we explored the level of circulating free fatty acids, cluster of differentiation 163 (CD163) macrophage marker, leptin and adiponectin. Thirty‐nine adults with type 1 diabetes and polyneuropathy were randomly assigned to 26 weeks of liraglutide or placebo treatment. Biopsies of subcutaneous tissue were formalin‐fixed stained with picrosirius red to visualize collagen or immunohistochemically stained for CD163. Serum concentrations of free fatty acids, CD163, leptin and adiponectin were assessed with immunoassays or multiplex panels. In comparison with placebo, liraglutide induced weight loss (3.38 kg, 95% CI −5.29; −1.48, P < 0.001), but did not cause any differences in cell size, distribution of CD163‐positive cells, pericellular fibrosis and serum levels of free fatty acids, CD163, leptin or adiponectin (all P < 0.1). Additionally, no associations between weight loss, cell size and serum markers were found (all P > 0.08). In conclusion, despite liraglutide's effect on weight loss, sustained alterations in subcutaneous adipose tissue did not seem to appear.
Background
Fibroblast growth factor 21 (FGF21) is a circulating hormone with pleiotropic metabolic effects, which is inactivated by fibroblast activation protein (FAP). Data regarding interaction between FGF21, FAP, and growth hormone (GH) are limited, but it is noteworthy that collagens are also FAP substrates, since GH potently stimulates collagen turnover.
Aim
To measure circulating FGF21 components, including FAP, in patients with acromegaly before and after disease control.
Methods
Eighteen patients with active acromegaly were studied at the time of diagnosis and ≥ 6 months after disease control by either surgery or medical treatment. Serum levels of total and active FGF21, β-klotho, FAP, and collagen turnover markers were measured by immunoassays. Expression of putative FGF21-dependent genes were measured in adipose tissue by reverse transcriptase-polymerase chain reaction, body composition assessed by dual-energy x-ray absorptiometry scan, and insulin sensitivity estimated with homeostatic model assessment of insulin resistance (HOMA-IR).
Results
Total FGF21, active FGF21 and β-klotho remained unchanged. Insulin sensitivity and body fat mass increased after disease control but neither correlated with active FGF21. Expression of FGF21-dependent genes did not change after treatment. FAP levels (µg/L) were markedly reduced after treatment [105.6 ± 29.4 vs 62.2 ± 32.4, P < 0.000]. Collagen turnover markers also declined significantly after treatment and ΔFAP correlated positively with ΔProcollagen Type I (P < 0.000) and Type III (P < 0.000).
Conclusion
1) Circulating FGF21 and β-klotho do not change in response to acromegaly treatment, 2) FAP concentrations in serum decrease after disease control and correlate positively with collagen turnover markers, and 3) FAP is a hitherto unrecognized GH target linked to collagen turnover.
Clinical Trials Registration
NCT00647179
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