Is the CCK2 receptor essential for normal regulation of body weight and adiposity?
Cholecystokinin (CCK) is a gastrointestinal satiety signal released from the duodenum to terminate feeding, via CCK1 receptors. CCK2 receptors are considered to be involved in anxiety. CCK2 receptor knockout mice have increased body weight and food intake. Little is known regarding the effects of CCK2 receptor deficiency on adipose distribution and hypothalamic feeding regulators such as neuropeptide Y (NPY), a powerful stimulator of feeding. Adult (10 week) CCK2 receptor knockout and wild-type mice were anaesthetized and killed by decapitation. Brain sections, organs and fat tissue were dissected. Plasma leptin, insulin and brain NPY content were measured by radioimmunoassay. Female CCK2 receptor knockout mice weighed more than control mice (22.0 +/- 0.2 vs. 19.9 +/- 0.4 g, P < 0.05), with this difference being less marked in male mice (26.4 +/- 0.4 vs. 25.6 +/- 0.6 g). Fat masses in all locations sampled were significantly smaller in CCK2 receptor knockout mice of both genders (P < 0.05), resulting in lower plasma leptin and insulin levels. NPY concentrations were significantly increased in arcuate nucleus and anterior hypothalamus in both male and female CCK2 receptor knockout mice, and total hypothalamic NPY content was increased by 7 and 9% in males and females, respectively (P < 0.05). CCK2 receptor deletion was associated with increased body weight and hypothalamic NPY content, but reduced fat masses and plasma leptin and insulin. Increased NPY might contribute to increased food intake in CCK2 receptor knockout mice. Further work needs to focus on the metabolic changes.
Chen
Hui
H
Department of Pharmacology, University of Melbourne, Victoria, Australia.
Kent
Stephen
S
Morris
Margaret J
MJ
D050154:Adiposity / Q000235:genetics / Q000502:physiology*; D000818:Animals; D001835:Body Weight / Q000235:genetics / Q000502:physiology*; D001923:Brain Chemistry / Q000502:physiology*; D003345:Corticosterone / Q000378:metabolism; D005260:Female; D007328:Insulin / Q000378:metabolism; D020738:Leptin / Q000378:metabolism; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D009478:Neuropeptide Y / Q000378:metabolism; D011863:Radioimmunoassay / Q000379:methods; D043887:Receptor, Cholecystokinin B / Q000172:deficiency / Q000502:physiology*; D012737:Sex Factors
D007328:Insulin; D020738:Leptin; D009478:Neuropeptide Y; D043887:Receptor, Cholecystokinin B; D003345:Corticosterone