CCK1 receptor is essential for normal meal patterning in mice fed high fat diet

Abstract

Cholecystokinin (CCK), released by lipid in the intestine, initiates satiety by acting at cholecystokinin type 1 receptors (CCK 1 Rs) located on vagal afferent nerve terminals located in the wall of the gastrointestinal tract. In the present study, we determined the role of the CCK 1 R in the short term effects of a high fat diet on daily food intake and meal patterns using mice in which the CCK 1 R gene is deleted. CCK 1 R -/-and CCK 1 R +/+ mice were fed isocaloric high fat (HF) or low fat (LF) diets ad libitum for 18 hours each day and meal size, meal frequency, intermeal interval, and meal duration were determined. Daily food intake was unaltered by diet in the CCK 1 R -/-compared to CCK 1 R +/+ mice. However, meal size was larger in the CCK 1 R -/-mice compared to CCK 1 R +/+ mice when fed a HF diet, with a concomitant decrease in meal frequency. Meal duration was increased in mice fed HF diet regardless of phenotype. In addition, CCK 1 R -/-mice fed a HF diet had a 75% decrease in the time to 1 st meal compared to CCK 1 R +/+ mice following a 6 hr fast. These data suggest that lack of the CCK 1 R results in diminished satiation, causing altered meal patterns including larger, less frequent meals when fed a high fat diet. These results suggest that the CCK 1 R is involved in regulating caloric intake on a meal to meal basis, but that other factors are responsible for regulation of daily food intake.

Food demand functions in mice

“…Tabarin et al (2007) also used a nose poke response (FR1) to deliver individual pellets to a trough, and reported ∼26 meals per day in B6/129 mice, a wild type mixed strain similar to that used in the present study. In contrast, using wild type mice of different strains but free delivery of pellets to a trough, other investigators consistently report 8-16 meals per day (Chi & Powley, 2003;Fox & Byerly, 2004;Donovan et al, 2007). Thus, meal size under free feeding or consummatory cost conditions in mice seems to be easily influenced by these types of variables, and as shown in the present study there may be substantial individual variability.…”

“…Methodologies in which discrete small food items are presented sequentially, such as in a standard operant test protocol, are particularly appealing because they minimize food spoiling behavior. A few such studies have appeared in the recent literature (e.g., Chi & Powley, 2003;Donovan, Paulino & Raybould, 2007;Fox & Byerly, 2004;Tabarin et al, 2007) but all have used a low and constant unit cost, so do not address economic considerations. We have previously reported results from operant protocols in normal and genetically obese mice (Vaughan, Moore, Haskell-Luevano, & Rowland, 2006;Vaughan & Rowland, 2003), but those studies did not examine systematic variation in cost parameters.…”

Modular genetic control of innate behaviors

“…For example, Brs3, which regulates the latency to intromit during mating, also regulates the latency to attack during territorial aggression; and Cckar, which controls female receptivity during mating, also regulates satiety during feeding [19]. Thus, one can not assert a one-to-one relationship between a genetic mutation and the observed behavioral phenotype without exhaustive phenotypic profiling, which is laborious and seldom carried out.…”

Central Nervous System Plus Autonomic Nervous System Disorders Responsible for Gastrointestinal and Pancreatobiliary Diseases

“…However, these hormones are coupled with the ANS mechanisms into a complex physiological interaction in such a way that any ANS disorder triggers the physiological unbalance responsible for different gastrointestinal and pancreatobiliary dysfunctions [5,6]. In addition, it has been demonstrated that CCK plays primordial physiological and pathophysiological roles in the motility of the colon [7,8]; in addition, this gastrointestinal hormone crosses the blood brain barrier, at which level it interacts with CCK receptors located at the dorsal raphe serotonergic nucleus DR-5HT and provokes satiety [9,10]. Underlying this physiological phenomenon is the reduction of both gastrointestinal motility and secretions and the inhibition of the distal colon motility.…”