Identification of genetic variants the CCKAR gene and based on body measurement and carcass quality characteristics in Qinchuan beef cattle (Bos taurus)

BACKGROUND: This study aimed to explore genetic polymorphisms of the CCKAR gene and their relationship with the growth and development of Qinchuan cattle which could be used as molecular markers for the improvement of the breeding of Qinchuan cattle. RESULTS: Here, we have identified seven single nucleotide polymorphisms (SNPs) at loci g. 1463 C>G; g. 1532 T>A; g. 1570 G>A; g. 1594 C>A; g. 1640 T>C; g. 1677 G>C; and g. 1735 C>T in the coding region of the bovine CCKAR gene. The frequencies identified on allelic and genotypic characteristics have shown that all seven SNPs diverged from the Hardy-Weinberg-Equilibrium. The SNP2, SNP3, SNP6 and SNP7 had the lowest polymorphism information content values, and remaining SNPs were found to be moderate (0.25 < PIC < 0.50). The genotype CG in SNP1 at loci g.1463 C>G had the greatest association with WH, HW, CD and CCF, while the genotype TA at the very same loci was associated with BFT, ULA and IMF content in Qinchuan cattle. The CCKAR gene expression level in adipose tissue, small intestine, liver and skeleton muscle was found to be higher, whereas, the expression level of mRNA in organs of other digestive system including reticulum, abomasum and omasum was moderate. Some expression of CCKAR mRNA was found in the large intestine, kidney and rumen. CONCLUSIONS: In summary, our finding suggested that the CCKAR gene could be used as a potential candidate for the improvement of carcass quality and body measurements of Qinchuan cattle.

Deep sequencing for cholecystokinin a receptor gene to get loci associated with schizophrenia / 中国医学科学院学报

<p><b>OBJECTIVE</b>To find the risk loci on cholecystokinin A receptor gene (CCKAR) - a schizophrenia candidate gene by using the deep sequencing and then analyze the variations.</p><p><b>METHODS</b>In the present study, 8 schizophrenia patients and 8 healthy controls were recruited. After DNA extraction from peripheral blood, we conducted deep sequencing on CCKAR region by HaloPlex Target Enrichment System (Agilent). We used Unphased software to exclude the false positive.</p><p><b>RESULTS</b>After deep sequencing, we got 103 loci, among which 30 were located in CCKAR gene. Besides, the SNP rs191275118 was found to be associated with schizophrenia.</p><p><b>CONCLUSIONS</b>A new variation that may be associated with schizophrenia was found. The deep sequencing is effective to find genetic variation.</p>

Reduction of Food Intake by Fenofibrate is Associated with Cholecystokinin Release in Long-Evans Tokushima Rats

Fenofibrate is a selective peroxisome proliferator-activated receptor alpha (PPARalpha) activator and is prescribed to treat hyperlipidemia. The mechanism through which PPARalpha agonists reduce food intake, body weight, and adiposity remains unclear. One explanation for the reduction of food intake is that fenofibrate promotes fatty acid oxidation and increases the production of ketone bodies upon a standard experimental dose of the drug (100~300 mg/kg/day). We observed that low-dose treatment of fenofibrate (30 mg/kg/day), which does not cause significant changes in ketone body synthesis, reduced food intake in Long-Evans Tokushima (LETO) rats. LETO rats are the physiologically normal controls for Otsuka Long-Evans Tokushima Fatty (OLETF) rats, which are obese and cholecystokinin (CCK)-A receptor deficient. We hypothesized that the reduced food intake by fenofibrate-treated LETO rats may be associated with CCK production. To investigate the anorexic effects of fenofibrate in vivo and to determine whether CCK production may be involved, we examined the amount of food intake and CCK production. Fenofibrate-treated OLETF rats did not significantly change their food intake while LETO rats decreased their food intake. Treatment of fenofibrate increased CCK synthesis in the duodenal epithelial cells of both LETO and OLETF rats. The absence of a change in the food intake of OLETF rats, despite the increase in CCK production, may be explained by the absence of CCK-A receptors. Contrary to the OLETF rats, LETO rats, which have normal CCK receptors, presented a decrease in food intake and an increase in CCK production. These results suggest that reduced food intake by fenofibrate treatment may be associated with CCK production.

Vagal Control of Satiety and Hormonal Regulation of Appetite

The paradigm for the control of feeding behavior has changed significantly. In this review, we present evidence that the separation of function in which cholecystokinin (CCK) controls short-term food intake and leptin regulate long-term eating behavior and body weight become less clear. In addition to the hypothalamus, the vagus nerve is critically involved in the control of feeding by transmitting signals arising from the upper gut to the nucleus of the solitary tract. Among the peripheral mediators, CCK is the key peptide involved in generating the satiety signal via the vagus. Leptin receptors have also been identified in the vagus nerve. Studies in the rodents clearly indicate that leptin and CCK interact synergistically to induce short-term inhibition of food intake and long-term reduction of body weight. The synergistic interaction between vagal CCK-A receptor and leptin is mediated by the phosphorylation of signal transducer and activator of transcription3 (STAT3), which in turn, activates closure of K+ channels, leading to membrane depolarization and neuronal firing. This involves the interaction between CCK/SRC/phosphoinositide 3-kinase cascades and leptin/Janus kinase-2/phosphoinositide 3-kinase/STAT3 signaling pathways. It is conceivable that malfunctioning of these signaling molecules may result in eating disorders.

The Effect of Gastrin and Cholecystokinin on the Growth of Pancreato-biliary Cancer Cell Lines

PURPOSE: Gastrin and cholecystokinin (CCK) have been reported to play a role in the development and growth stimulation of gastrointestinal cancers including pancreatic cancer. METHODS: We investigated the effects of gastrin and CCK on the growth of pancreatic and biliary tract cancer cell lines established at the Cancer Research Institute of Seoul National University College of Medicine, using reverse transcription-polymerase chain reaction (RT-PCR) and slot blot hybridization, to examine the expressions of hormonal receptors in these cell lines. RESULTS: Of the six biliary tract, and five pancreatic, cancer cell lines, SNU-308 showed a growth stimulated effect due to gastrin-17, as did SNU-478 to both gastrin-17 and CCK-8. The trophic effect of these two hormones was completely blocked by specific antagonists (L-365, 260 for gastrin and L-364, 718 for CCK). The other cell lines did not respond to either the gastrin or the CCK. From the RT-PCR, the presence of the CCK-A receptor and the CCK-B/gastrin receptor mRNA was detected in all the biliary and pancreatic cancer cell lines. From the slot blot hybridization, although the cell lines that responded to the hormones showed high level of expression for receptor mRNA, so did some of those not responding to the hormones. CONCLUSION: This study suggests that gastrin and CCK exert a trophic action on some biliary tract cancers due to their specific receptors. However, further studies investigating the functional and structural variation among these receptors, in relation to their subtypes and mutation/polymorphism are requisite prior to their clinical usage for adjunctive hormonal or antihormonal therapy can be recommended.