Tumor-associated energy homeostasis: hepatoblastoma and neuroblastoma affect glucose and lipid metabolism as well as ghrelin, GLP-1, and PYY in nude rats.

BACKGROUND

The "metabolic competition" for nutrients between cancer cells and the patient has emerged as an important research area. For pediatric oncology, it remains unclear whether the neuroendokrine regulation of appetite by gastrointestinal hormones such as ghrelin "eat", GLP-1 (glucagon-like peptide, "do not eat"), and PYY (peptide tyrosine-tyrosine, "do not eat") is influenced by tumor growth.

METHODS

In a prospective randomized study, human hepatoblastoma (HB) and neuroblastoma (NB) cells (3 × 10(6)) were transplanted into the abdominal wall of immune-incompetent (nu/nu) rats (ethic committee approval: TVV43/11). Sham-operated animals received cell culture medium only. Tumor growth was allowed for 8 weeks. Then, all the animals underwent a 2-hour oGTT (oral glucose tolerance test) and were assessed for serum levels of glucose, insulin, ghrelin, GLP-1, and PYY. Finally, all tumor masses and adipose tissues were excised and calculated.

RESULTS

Total body weight (including tumor masses) differed for HB (329+31 g), but not for NB (358+22 g) compared with Sham (361+35 g). Subcutaneous adipose tissue was significantly decreased for both the tumor groups (HB=2.6 g, NB=2.1 g, and Sham=3.5 g). Only for NB, fasting glucose (3.4 + 0.6 mmol/L) and insulin (0.89+0.11 ng/mL) levels were significantly decreased compared with Sham (4.4+0.6 mmol/L; 1.19+0.36 ng/mL) only. During the oGTT (all data calculated as area under the curve, AUC) glucose levels were significantly increased for HB (104 ± 10) and NB (102 ± 13) compared with Sham (84 ± 3), but insulin levels remained similar for either group. Triglyceride levels were increased for HB (0.51 mmol/L) and especially NB (0.73 mmol/L) compared with Sham (0.34 mmol/L). Inflammatory parameters did not differ between the groups. Total ghrelin levels were significantly increased for NB (111 ± 10) and altered for HB (102 ± 15) compared with Sham (84 ± 8). Vice versa GLP-1 was statistically decreased in HB (92 ± 7) and NB (88 ± 12) compared with Sham (127 ± 13). Finally, PYY levels were nonsignificantly reduced for HB (117 ± 5) and NB (120 ± 4) compared with Sham (146 ± 12).