Energy Metabolism and Turnover Are Increased in Mice Lacking the Cholecystokinin-B Receptor

Abstract

Cholecystokinin (CCK) is an important gastrointestinal hormone as well as a neurotransmitter. Two types of CCK receptors, types A and B, have been identified. The CCK-A receptor is involved in satiety, food intake and behavior, whereas the B receptor is involved in anxiety. We recently produced CCK-A, -B and AB receptor knockout mice to study the role of these receptors in energy metabolism. Daily energy intake and expenditure were significantly greater in CCK-BR(-/-) and CCK-AR(-/-)BR(-/-) mice than CCK-AR(-/-) and wild-type [CCK-AR(+/+)BR(+/+)] mice. Relative liver and kidney weights (g/kg body) were significantly greater in CCK-AR(-/-)BR(-/-) mice than in wild-type mice. Energy metabolism and energy turnover were increased in mice with a disruption of the CCK-BR gene, although the underlying mechanism is unknown.

Lack of Ghrelin Secretion in Response to Fasting in Cholecystokinin-A (-1), -B (-2) Receptor–Deficient Mice

“…CCK-AR binds sulfated CCK with 500-to 1,000-fold higher affinity than gastrin and nonsulfated CCK, though the CCK-BR interacts with gastrin and CCK with almost the same affinity. Thus the phenotype of the CCK(-/-)gastrin(-/-) mice reported by Friis-Hansen et al [15] resembles that of the CCK-AR(-/-)BR(-/-) mice developed in our laboratory [18,19].…”

“…In previous experiments, we usually observed a lower body weight in CCK-AR(-/-)BR(-/-) mice than in other genotypes [18,19]. Rodents have nocturnal habits; thus they eat during nighttime and sleep during daylight.…”

“…Rodents have nocturnal habits; thus they eat during nighttime and sleep during daylight. In a previous report [18], we examined food intake during the nighttime and found that CCK-BR(-/-) and CCK-AR(-/-)BR(-/-) mice showed higher food intake than wild-type or CCK-AR(-/-) mice did. Moreover, we observed higher energy consumption during a 24-h period in CCK-BR(-/-) and AR(-/-)BR(-/-) mice than in CCK-AR(-/-) or wild-type mice.…”

“…That is, mice without CCK-BR [CCK-BR(-/-) and AR(-/-)BR(-/-) mice]showed enhanced energy turnover with higher food intake during the nighttime and higher energy consumption over a 24-h period resulting in constant body weight. Therefore it is possible that the absence of food intake during the nighttime together with the higher energy consumption of these mice may be responsible for the lower body weight of CCK-BR(-/-) and CCK-AR(-/-)BR(-/-) mice, although we determined only overall energy expenditure without distinguishing between daylight and nighttime expenditures [18].…”

Disturbance of Response to Acute Thermal Pain in Naturally Occurring Cholecystokinin-A Receptor Gene Knockout Otsuka Long-Evans Tokushima Fatty (OLETF) Rats

“…To distinguish the functional role of CCK-AR from that of CCK-BR, we also used CCK-BR(−/ −) and CCK-AR(−/ −)BR(−/ −) mice. The progenitor strains were C57BL / 6J and more than seven generations of back-crossing were performed (3,19,20). These mice are all viable and fertile into adulthood.…”