Endocrine Abstracts

Background: The hypothalamus is a critical area of the brain involved in the regulation of appetite. Cerebellin1 (Cbln1) is a highly conserved 16 amino acid neuropeptide. High levels of Cbln1 mRNA expression are found in specific hypothalamic areas involved in appetite regulation.

Aim: To examine the effects of Cbln1 on food intake in rodents.

Methods: 1. Ad libitum fed rats were injected intracerebroventricularly (ICV) with Cbln1 (1, 3, 10 & 30 nmol) and food intake measured for 24 h post injection (n=10/group).

2. Behavioural analysis was carried out for 1 h post ICV administration of Cbln1 (30 nmol).

3. To investigate a possible mechanism of action, the effects of Cbln1 (10, 100 & 1000 nM) on the release of orexigenic and anorexigenic neuropeptides from ex vivo rat hypothalamic explants was determined using radioimmunoassay (n=15/group).

4. To determine whether Cbln1 has a physiological capacity in regulating food intake, hypothalamic Cbln1 mRNA and peptide levels were determined following 12 and 24 h fasting in rats using quantitative PCR and radioimmunoassay, respectively (n=15/group).

Results: 1. ICV administration of Cbln1 to rats resulted in a significant increase in food intake 1 h post-injection (0.34±0.08 g (saline); 0.72±0.28 g (3 nmol); 1.68±0.51 g (10 nmol); P<0.01; 1.71±0.53 g (30 nmol) P<0.05).

2. ICV administration of Cbn1 did not cause adverse behavioural effects.

3. Cbln1 (10, 100 & 1000 nM) resulted in a significant increase in the release of the orexigenic factor, neuropeptide Y (NPY) (199, 144 and 126% of basal release, respectively, P<0.05). Cbln1 had no effect on the release of the orexigenic neuropeptide, agouti related peptide or anorexigenic neuropeptides, cocaine and amphetamine regulated transcript or alpha melanocyte stimulating hormone.

4. Hypothalamic Cbln1 mRNA and peptide levels were not significantly different in fed compared to fasted animals.

Conclusion: Our data identifies Cbln1 as a novel orexigenic factor and potential new therapeutic target for the development of anti-obesity agents.