CCK Concentrations Research Articles

PSLBII-23 Effects of alternative production systems on growth and circulating blood profiles in Berkshire grower pigs

Abstract In this study, we compared the growth performance and circulating blood profiles of Berkshire grower pigs maintained in two different alternative swine production systems, the dry-lot production system, and the hoop structure production system. This study was conducted during a 75-d period spanning from May to July at the North Carolina Agricultural and Technical State University Swine Facility in Greensboro, N.C. Protein expression profiles associated with growth (FGF-19, PDGF-BB, IGF-1), feed intake (CCK), stress (cortisol) and the ability to handle oxidative stress (T-AOC) were analyzed in blood plasma obtained from 24 Berkshire nursery/grower pigs. Berkshire pigs (n = 12) were managed in a 12.19 m x 18.28 m hoop structure with the end walls removed for ventilation and a straw deep bedding system. Twelve additional Berkshire nursery/grower pigs were managed in a 0.08-ha dry-lot. These animals were provided with a canopy for shade and a wallowing area for evaporative cooling. All animals were provided with ad libitum ration and water. Individual body weights (BW) and blood samples were collected at 25-d intervals throughout the 75-d trial, culminating in three different time points. Plasma was isolated from the blood samples and used for ELISA and colorimetric assays. The BioTek 800 TS absorbance reader and Gen5 Microplate Reader and Imager software (Agilent Technologies, Inc., Santa Clara, CA) were used to obtain and calculate the optical densities of the plasma samples, respectively. The data were analyzed using the two-way ANOVA feature of JMP 17.2.0 software (SAS Institute, Inc., Cary, NC) with production system and growth period considered fixed variables, while either growth rate or protein concentration were considered as the response variable. There were four significant treatment effects observed (P < 0.05). Significantly greater concentrations of IGF-1, CCK, and T-AOC were detected in the plasma collected from Berkshire pigs managed in the dry-lot. Whereas those managed in the hoop structure production system had heavier BW. The results show that exposing pigs to higher temperatures can reduce feed intake and growth rates. However, this same stress elicits the release of hormones that promote growth, while enhancing the total antioxidant capacity in these animals. The results support the adoption of the hoop structure production system over the dry-lot production system when managing swine in regions that experience higher temperatures.

Early Enteral Nutrition Does Not Cause Excessive Inflammatory Response in Veno-Arterial Extracorporeal Membrane Oxygenation Patients

Background: To evaluate the safety between early enteral nutrition (EN) and parenteral nutrition (PN) by observing changes in inflammatory cytokines and gastrointestinal hormones in veno-arterial extracorporeal membrane oxygenation (VA ECMO) patients. Methods: This study was a prospective, observational study that enrolled patients receiving VA ECMO treatment from 1 January 2020 to 31 December 2023. Patients were enrolled in an EN group or a PN group according to the inclusion criteria. The concentration of interleukin-1β (IL-1β), interleukin-6 (IL-6), interleukin-10 (IL-10), and tumor necrosis factor α (TNF-α) on the first five days of VA ECMO treatement were tested in both groups. Serum concentrations of Motilin (MOT), Gastrin (GAS), Cholecystokinin (CCK), and Calcitonin gene-related peptide (CGRP) were measured for the EN group. Student t test or Fisher test was used to compare the difference between the two groups. Results: 28 patients were enrolled in this study; 16 in the EN group and 12 in the PN group. The baseline characteristics were comparable between the two groups. The concentration of IL-1β in the EN group was significantly lower than that of the PN group on day 3 and day 4 (day 3: 0.65 ± 0.17 pg/mL vs. 0.93 ± 0.09 pg/mL, p < 0.01, day 4: 0.52 ± 0.16 pg/mL vs. 0.74 ± 0.12 pg/mL, p < 0.01). The concentration of IL-6 and TNF-α in the EN group were also significantly lower than in the PN group on day 3 and day 4. There was no statistical difference in IL-10 serum concentration between the EN group and the PN group from day 1 to day 5. On day 3, the concentration of MOT, GAS and CCK reached the highest level and then gradually decreased. Conclusions: Implementation of early EN in patients receiving VA ECMO does not cause significant elevation of pro-inflammatory cytokines with an excessive inflammatory response.

Rynchopeterine inhibits the formation of hypertrophic scars by regulating the miR-21/HIF1AN axis

Hypertrophic scar (HS) is a fibroproliferative skin disease characterized by abnormal wound healing and pathological excessive fibrosis of the skin. Currently, the molecular mechanism of the disease is still largely unknown, and there is no effective drug treatment. In this study, we explored the effect of Rynchopeterine on the formation of HS. HS fibroblasts (HSFs) were isolated from the HS tissues of patients recovering from severe burns. After treating HSFs with different concentrations of Rynchopeterine, CCK-8, EdU, and Annexin V-FITC/PI assays were used to detect the proliferation, apoptosis, and contractile ability of HSFs. RT-qPCR and Western blotting were performed to evaluate the effect of Rynchopeterine on the expression of miR-21 and hypoxia-inducible factor 1-alpha subunit suppressor (HIF1AN). The dual-luciferase reporter gene was used to verify the targeting relationship between miR-21 and HIF1AN. Rynchopeterine reduced the expression of Col1a2, Col3a1, and α-SMA, inhibited proliferation and contraction of HSFs, and increased apoptosis in a dose-dependent manner. miR-21 was highly expressed in HS tissues and HSFs, and Rynchopeterine could inhibit miR-21 expression. Overexpression of miR-21 and knockdown of HIF1AN increased proliferation, activation, contraction, and collagen synthesis of HSFs, and inhibited their apoptosis. In vivo, Rynchopeterine could reduce the collagen content of the dermis and the positive ratio of PCNA and α-SMA. Rynchopeterine is a good therapeutic agent for HS, which up-regulates the expression of HIF1AN by inhibiting miR-21, thereby inhibiting the formation of HS.

Cholecystokinin 1 Receptor Is Activated Permanently in Photodynamic Action

In contrast to agonist activation that is reversed after washout of agonist, we have found that cholecystokinin 1 receptor (CCK1R) is activated permanently by singlet oxygen in type II photodynamic action, the G Protein Coupled Receptor (GPCR) Activated By Singlet Oxygen is named GPCR-ABSO. CCK1R ectopically expressed in cell lines is activated in photodynamic action with photosensitizer sulphonated aluminum phthalocyanine (SALPC) or with genetically encoded protein photosensitizers (such as miniSOG, KillerRed) to trigger persistent calcium oscillations which are not washed out. Such permanent photodynamic CCK1R activation is seen also in freshly isolated pancreatic acini, which is inhibited by CCK1R antagonist. Photodynamic CCK1R activation is physiological in intensity, triggering calcium oscillations similar in frequencies to those induced by physiological CCK concentrations (10 - 100 pM). The molecular mechanisms for such permanent photodynamic activation of CCK1R at the physiological level are three-fold. When membrane proteins prepared from isolated rat pancreatic acini are subject to Western blot, CCK1R is found to be present as both dimers and monomers. After photodynamic action with SALPC at an intensity that would trigger persistent calcium oscillations in live cells, the resting receptor dimer is converted quantitatively to monomer, similar to agonist stimulated CCK1R monomerization revealed by bioluminescence resonance energy transfer (BRET) method in rat CCK1R-expressing COS cells, suggesting that photodynamic CCK1R activation we have demonstrated is likely quite physiological. Whilst CCK1R is activated by singlet oxygen in photodynamic action, the M3 acetylcholine receptor is not affected. However, when TM3 of CCK1R is transplanted to M3R to replace TM3 of M3R, the chimeric receptor M3R-TM3CCK1R becomes activatable in photodynamic action, after tagging with miniSOG. The calculated extent of miniSOG photodynamic activation of M3R, chimeric M3R-TM3CCK1R, and CCK1R are 0%, 65%, 100% respectively. Comparative studies with pancreatic acini isolated from the rat, mouse and Peking duck found that sensitivity for photodynamic CCK1R activation is, in descending order: mouse > rat > Peking duck, the same order of the size of structure-free region of intracellular loop 3 (ICL3). Other than CCK1R, CCK2R is photodynamically activated also, after tagging with protein photosensitizer miniSOG. CCK1R and CCK2R are known to be involved in vital physiological functions: pancreatic secretion, satiety sensation, sinoatrial node pace-making, memory formation and storage, and others. Our work implies that all these and other physiological functions might be modulated in vivo by photodynamic CCK1R activation. The fact that such property of permanent photodynamic activation could be transplanted from CCK1R to other GPCR such as M3R suggests that photodynamic activation of GPCR could be used to tease apart the roles and functions of vast numbers of GPCR. Other functional proteins such as NAD(P)H oxidase 2, BK/Slo channel, CaMKII, riboflavin transporter (SLC52A1/RFVT1), might also be photodynamically activated permanently. This work was supported by The Natural Science Foundation of China (NSFC, Grant Nos. 31971170 and 32271278). This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

Embelin enhances the osteogenic potential of LPS-induced periodontal ligament stem cells by activating AMPK and SIRT1

Purpose: To investigate the role of embelin in periodontal ligament stem cells (PDLSCs) in an in vitro model of periodontitis.Methods: Lipopolysaccharide (LPS)-stimulated PDLSCs was used to construct a periodontitis cell model. PDLSCs in the treatment group were pretreated with different concentrations of Embelin, and CCK-8 and TUNEL staining were used to analyze cell viability and apoptosis. Enzyme-linked immunosorbent assay (ELISA) kits were used to evaluate the levels of inflammatory cytokines (TNF-α, IL-1β, IL-6, and MCP-1) while reactive oxygen species levels were assessed by 2',7'- dichlorodihydrofluorescein diacetate (DCFH-DA) staining. Subsequently, osteogenic marker, ALP activity and protein expression levels of Runx2, OCN and BMP-2 in PDLSCs were evaluated by western-blot assay; AMPK and SIRT1 levels were also determined using Western blot assay.Results: Embelin pretreatment inhibited PDLSCs apoptosis, inflammatory factors, and oxidative stress, but up-regulated ALP, Runx2, OCN, and BMP-2 levels (p < 0.05). In addition, AMPK phosphorylation and SIRT1 protein levels were regulated by embelin (p < 0.05).Conclusion: Embelin exerts anti-inflammatory, anti-oxidative and osteogenic differentiation effects in LPS-induced PDLSCs cells in vitro by activating AMPK/SIRT1 signaling. Therefore, the compound has potentials for use in the management of periodontitis.

Primary weight loss failure after Roux-en-Y gastric bypass is characterized by impaired gut-hormone mediated regulation of food intake

Background/ObjectivesAfter Roux-en-Y gastric bypass (RYGB) a subset of patients never obtain excess BMI loss (EBMIL) > 50% and are categorized as having primary weight loss (WL) failure. We hypothesized that postprandial concentrations of glucagon-like peptide 1 (GLP-1) and peptide YY (PYY) would be lower in patients with primary WL failure compared with patients with successfully maintained WL. Furthermore, that inhibition of gut hormone secretions would increase ad libitum food intake less in patients with primary WL failure.Subjects/MethodsTwenty women with primary WL failure (LowEBMIL < 50%) were individually matched to twenty women with successful WL (HighEBMIL > 60%) on age, preoperative BMI and time from RYGB. On separate days performed in a random order, patient-blinded subcutaneous injections of octreotide or saline (placebo) were followed by a fixed breakfast and an ad libitum lunch with blood sampling for appetite regulating hormones and Visual-Analogue-Scale (VAS)-scoring of hunger/satiety. Furthermore, participants underwent gene variant analysis for GLP-1, PYY and their receptors, indirect calorimetry, dual-energy X-ray absorptiometry (DXA)-scans, 4-days at-home food registration and 14-days step counting.ResultsOn placebo days, postprandial GLP-1, PYY and cholecystokinin (CCK) concentrations were similar between groups after breakfast. Fasting ghrelin was lower in LowEBMIL, but the postprandial suppression was similar. LowEBMIL had lower satiety VAS-scores and less suppression of hunger VAS-scores. Gene variants did not differ between groups. Octreotide diminished GLP-1, PYY, CCK and ghrelin concentrations in both groups. Octreotide did not affect ad libitum food intake in LowEBMIL (−1% [−13, 12], mean [95%CI]), while food intake increased in HighEBMIL (+23% [2,44]).ConclusionsPrimary WL failure after RYGB was not characterized by impaired secretions of appetite regulating gut hormones. Interestingly, inhibition of gut hormone secretions with octreotide only increased food intake in patients with successful WL post-RYGB. Thus, an impaired central anorectic response to gut hormones may contribute to primary WL failure after RYGB.

Boar sperm motility is modulated by CCK at a low concentration of bicarbonate under capacitation conditions.

In a previous study, our group detected the cholecystokinin (CCK) protein in the porcine oviduct. This fact, together with the involvement of CCK in the regulation of sperm protein tyrosine phosphorylation by the modulation of HCO3 - uptake (in mice and humans) suggests a role for CCK during sperm capacitation. Therefore, on the one hand, the expression of CCK receptors (CCK1R and CCK2R) on boar testes has been investigated and probed; on the other hand, boar spermatozoa (from seminal doses of 1-day and 5-day storage) were exposed to different concentrations of CCK (0-control, 25 or 50 μM) in a medium supporting capacitation supplemented with 0, 5 or 25 mmol/L of HCO3 - for 1 h at 38.5°C. Sperm motion (total and progressive motility), kinetic parameters, viability, acrosome status, and mitochondrial activity were determined. No differences between groups (0, 25 or 50 μM of CCK) were observed when HCO3 - was absent in the media (p > .05). However, the results showed that when the media was supplemented with 5 mmol/L HCO3 - in 1-day seminal dose storage, the linearity index (LIN, %), straightness index (STR, %) and oscillation index (WOB, %) (sperm kinetics parameters) increased in the presence of CCK regardless the concentration (p < .05). Nevertheless, CCK in sperm from 5-day storage only increased the WOB parameter in comparison to the control (p < .05). Furthermore, the average amplitude of the lateral displacement of the sperm head (ALH, μm) and curvilinear velocity (VCL, μm/s) decreased when CCK was present, depending on its concentration and sperm aging (1-day vs. 5-days) (p < .05). In the case of the media supporting capacitation supplemented with 25 mmol/L HCO3 - , any differences were observed except for sperm viability in the 5-day seminal doses, which increased in the 50 μM-CCK group compared to the control (p < .05). In conclusion, these data suggest an implication of CCK protein during sperm capacitation under low bicarbonate concentration increasing the sperm linear trajectory.

Nothobranchius as a model for anorexia of aging research: an evolutionary, anatomical, histological, immunohistochemical, and molecular study

BackgroundAnorexia of aging, defined as a decrease in appetite and a preponderant loss of body weight occurring in late life, is one of the most common diseases affecting older people.The peptide hormone cholecystokinin (Cck) is known to play a key role in regulating food intake and satiety in higher vertebrates. In humans as well as in rats, an increased concentration of Cck was described as the basis of appetite loss in elderly. However, the role of increased plasma Cck concentrations in mediating the age-related decrease in appetite remains to be established.Although in vitro studies are an excellent resource for investigating aging, the use of a model organism that shares and imitates the human physiological processes guarantees a better understanding of the in vivo mechanisms.African annual fishes from the genus Nothobranchius are emerging as a prominent model organism in biogerontology and developmental biology due to their short captive lifespan.Therefore, in the current study, we aimed to investigate the possibility of using the genus Nothobranchius to model the anorexia of aging and their potential contribution to better understanding the pathway by which Cck induce appetite loss in older people providing a comparative/evolutionary localization of the current study model among the aging canonicals models, the morphology of its gastrointestinal tract and its Cck expression pattern. MethodsThe comparative/evolutionary investigation was conducted using the NCBI blastp (protein-protein BLAST) and NCBI Tree Viewer. The macroscopic morphology, histological features, ultrastructural organization of Nothobranchius rachovii gastrointestinal tract were investigated using stereomicroscope, Masson's trichrome and alcian blue–PAS staining, and transmission electron microscopy, respectively.The cck expression pattern was studied through immunofluorescence labeling, western blotting, and quantitative RT-PCR. ResultsThe intestine was folded into different segments divided into an anterior intestine made of a rostral intestinal bulb and an intestinal annex of lower diameter, mid and posterior intestine. The gradual transition from the rostral intestinal bulb to the posterior intestine sections's epithelium is characterized by a gradual reduction in the striated muscular bundles, villi height, and goblet mucous cells count. The lining epithelium of the intestinal villi was characterized by a typical brush border enterocytes full of mitochondria. Moreover, Cck expression was detected in scattered intraepithelial cells concentrated in the anterior tract of the intestine. ConclusionsOur study introduces Nothobranchius rachovii as a model for anorexia of aging, giving the first bases on the gastrointestinal tract morphology and cck expression pattern. Future studies on young and elderly Notobranchius can divulge the contribution of cck in the mechanisms of anorexia associated with aging.

Liraglutide changes postprandial responses of gut hormones involved in the regulation of gallbladder motility.

Liraglutide treatment is associated with gallbladder-related disorders and has been shown to delay postprandial gallbladder refilling. The gut hormones cholecystokinin (CCK), fibroblast growth factor 19 (FGF19) and glucagon-like peptide 2 (GLP-2), are known to regulate gallbladder motility and may be implicated in gallbladder-related disorders associated with liraglutide treatment. In a double-blind, 12-week trial, 52 participants [50% male, age 47.6 ± 10.0 years, body mass index 32.6 ± 3.4kg/m2 (mean ± standard deviation)] with obesity were randomized 1:1 to once-daily subcutaneous liraglutide (escalated from 0.6mg to 3.0mg once-daily) or placebo. During liquid meal tests performed at baseline, after the first dose and following 12 weeks of treatment, we evaluated postprandial gallbladder dynamics and plasma responses of CCK, FGF19 and GLP-2. Liraglutide reduced postprandial FGF19 after the first dose [area under the curve (AUC)0-240 min 24.8 vs. 48.0min× ng/ml, treatment ratio (TR) (95% confidence interval) 0.52 (0.39; 0.69)] and following 12 weeks of treatment [AUC0-240 min 33.7 vs. 48.5ng/ml × min, TR 0.69 (0.52; 0.93)]. Liraglutide also reduced postprandial GLP-2 responses (AUC0-240 min 3650 vs. 4894 min× pmol/L, TR 0.75 (0.62; 0.90)] following the first dose as well as after 12 weeks [AUC0-240 min 3760 vs. 4882 min× pmol/L, TR 0.77 (0.60; 0.99)]. Liraglutide increased postprandial responses of CCK after the first dose [AUC0-240 min 762 vs. 670 min× pmol/L; TR 1.14 (0.97; 1.33)] and following 12 weeks of treatment [AUC0-240 min 873 vs. 628 min× pmol/L; TR 1.39 (1.12; 1.73)]. Compared with placebo, treatment with liraglutide decreased postprandial FGF19 and GLP-2 concentrations and increased postprandial CCK concentrations, which may explain the delayed postprandial gallbladder refilling observed in individuals with obesity treated with liraglutide.

Leucine (and lysine) increased plasma levels of the satiety hormone cholecystokinin (CCK), and phenylalanine of the incretin glucagon-like peptide 1 (GLP-1) after oral gavages in pigs.

Excess dietary amino acids (AA) has been associated with reduced feed intake, increased satiation, and extended satiety in pigs. Recent ex vivo studies suggested that satiety peptide cholecystokinin (CCK) and insulinotropic glucagon-like peptide 1 (GLP-1), mediated the anorexigenic or insulinotropic effects of Lys, Glu, Phe, Ile, and Leu. However, the ex vivo model limitations require validation in vivo. The aim of the present study was to assess the effect of orally administered AA in vivo in pigs. It was hypothesized that oral Lys, Ile, and Leu have an anorexigenic effect via CCK, while Glu and Phe have an insulinotropic effect increasing circulating levels of GLP-1. Eight entire male pigs (Landrace × Large White) of 18.23 ± 1.06 kg of body weight were administered an oral gavage of water (control) or a 3 mmol/kg of Glu, Ile, Leu, Lys, Phe, or glucose (positive control for GLP-1 release) following an overnight fasting during 5 consecutive days using an incomplete latin square design. Blood samples were collected from the jugular vein before (-5 min, baseline value) and after the gavage (5, 15, 30, 60 and 90 min) to assess CCK and GLP-1 plasma levels. Pigs administered the oral gavage of Leu (P < 0.05), or Lys (P < 0.1) had increased levels of plasma CCK from 0 to 90 min post-gavage when compared to the control. A strong association (P < 0.001) was observed between GLP-1 plasma levels with Phe intake. The impact was significant starting 30 min post-gavage and was sustained until the end of the experiment (90 min post-gavage). Glucose administration increased GLP-1 early after the intake at the 5 min mark (P < 0.1). A positive correlation (P < 0.05, r = 0.89) driven by the impact of Phe at the 60 to 90 min post-gavage was identified between CCK and GLP-1 indicating feedback mechanisms between proximal and distal small intestine. In conclusion, oral gavages of Leu and Lys increased anorexigenic hormone CCK plasma levels in pigs. Phe caused a significant long-lasting increase in incretin GLP-1 plasma levels. Blood CCK and GLP-1 concentrations in Phe gavaged pigs were positively correlated indicating a potential feedback mechanism between proximal (CCK) and distal (GLP-1) small intestine. The present results are compatible with the known anorexigenic effects of excess dietary Leu and Lys, and the insulinotropic effect of Phe in pigs. These results demonstrate the relevance of accurate feed formulation practices particularly in post weaning pigs.

CCK regulates osteogenic differentiation through TNFα/NF-κB in peri-implantitis

Peri-implantitis is characterized by peri-implant mucositis and alveolar bone resorption. This study investigated cholecystokinin (CCK) expression and the mechanism underlying its involvement in peri-implantitis. mRNA sequencing was performed using the Gene Expression Omnibus database GSE106090. Human bone marrow mesenchymal stem cells (hBMSCs) were pretreated with various concentrations of CCK (0, 10, 30, or 100 nM) for 1 hour before induction in osteogenic differentiation medium for 2 weeks. Alkaline phosphatase (ALP) activity was determined, and the cells were stained with alizarin red. The expression levels of TNFα and the osteogenic markers ALP, RUNX2, and OCN were measured using quantitative real-time PCR. TNFα, phosphorylated P65, and total P65 levels were determined by western blot. Compared with healthy individuals, 262 and 215 genes were up- and down-regulated, respectively, in the periodontal tissues of patients with peri-implantitis. CCK expression was significantly upregulated in patients with peri-implantitis. CCK reduced ALP activity, osteogenic differentiation, and levels of the osteogenic markers ALP, RUNX2, and OCN. Moreover, CCK promoted levels of TNFα and phosphorylated P65, which is a marker of activation for the NF-κB inflammatory pathway. CCK regulates osteogenic differentiation through the TNFα/NF-κB axis in peri-implantitis.

Increased Meal Size but Reduced Meal-Stimulated Plasma Cholecystokinin Concentrations in Women With Obesity.

To better understand the physiological basis of obesity in women, we investigated whether obesity or menstrual cycle phase affects laboratory test-meal size or meal-stimulated plasma cholecystokinin (CCK) concentration. Women with healthy weight (body mass index [BMI] of 18.5-24.9 kg/m2, N = 16) or obesity (BMI 30-39.9 kg/m2, N = 20) were tested once in the late-follicular or peri-ovulatory phase (LF/PO) and once in the mid-luteal phase (ML). Meals of ham sandwiches were offered and blood was sampled. Menstrual cycle phases were verified with participants' reports of menses and measurements of progesterone and luteinizing hormone (LH) concentrations. Women with obesity ate significantly larger meals than women with healthy weight, (mean, 711 [95% CI, 402-1013] kJ, P = 0.001, during the LF/PO and 426 [105-734] kJ, P = 0.027, larger during the ML). Women with healthy weight ate smaller meals during LF/PO than ML (decrease, 510 [192-821 kJ], P = 0.008), but women with obesity did not (decrease, 226 [-87-542] kJ, P = 0.15). CCK concentrations 18 to 30 minutes after meal onset were lower in women with obesity than in women with healthy weight during LF/PO (3.6 [3.1-4.1] vs 6.1 [4.5-7.7] pmol/L; P = 0.004), but not during ML, with a significant interaction effect (1.8 [1.2-2.4] pmol/L, P = 0.048). Women with obesity consumed larger meals than women with healthy weight but displayed reduced meal-stimulated plasma CCK concentrations. These data are consistent with the hypothesis that a defect in CCK secretion compromises satiation in obese women and contributes to the development or maintenance of obesity.

Oral Erythritol Reduces Energy Intake during a Subsequent ad libitum Test Meal: A Randomized, Controlled, Crossover Trial in Healthy Humans.

The impact of oral erythritol on subsequent energy intake is unknown. The aim was to assess the effect of oral erythritol compared to sucrose, sucralose, or tap water on energy intake during a subsequent ad libitum test meal and to examine the release of cholecystokinin (CCK) in response to these substances. In this randomized, crossover trial, 20 healthy volunteers received 50 g erythritol, 33.5 g sucrose, or 0.0558 g sucralose dissolved in tap water, or tap water as an oral preload in four different sessions. Fifteen minutes later, a test meal was served and energy intake was assessed. At set time points, blood samples were collected to quantify CCK concentrations. The energy intake (ad libitum test meal) was significantly lower after erythritol compared to sucrose, sucralose, or tap water (p < 0.05). Before the start of the ad libitum test meal, erythritol led to a significant increase in CCK compared to sucrose, sucralose, or tap water (p < 0.001). Oral erythritol given alone induced the release of CCK before the start of the ad libitum test meal and reduced subsequent energy intake compared to sucrose, sucralose, or tap water. These properties make erythritol a useful sugar alternative.

Resting and postpradial serum cholecystokinin concentrations and evaluation of the effect of seeing and/or smelling food on serum cholecystokinin and bile acid concentrations in healthy dogs

Serum bile acids concentrations rise postprandially. However, some dogs show paradoxical serum bile acids results with higher pre-prandial than post-prandial concentrations. The aim of this study was to evaluate serum cholecystokinin (CCK) concentrations and determine whether they correspond to paradoxical serum bile acids concentrations. In addition, seeing and smelling food was investigated as a possible cause for paradoxical serum bile acids results. Eight healthy dogs owned by volunteers enrolled in this experimental study. Food was withheld from the dogs for 12 h with great care not to expose them to any sight or smell of food. Blood samples were collected at 0, 30, 60, 120, 180, 240, 480 and 720 min after feeding. Food was then withheld again for 24 h, and blood samples were collected at 0, 30, 60, 120, 180, 240, 480 and 720 min after seeing and smelling food. After feeding, serum CCK concentrations increased, but paradoxical serum CCK concentrations were observed in some of dogs, but only one of those had also paradoxical serum bile acids concentrations. After seeing and smelling food, serum CCK and serum bile acids concentrations did not significantly increase. In conclusion, paradoxical serum CCK concentrations can occur in some healthy dogs after feeding. However, no correlation with paradoxical serum bile acids concentrations was found. Seeing or smelling food are unlikely causes for paradoxical serum bile acids concentrations. Additional studies are warranted to further evaluate the relationship of serum CCK and bile acids concentrations in healthy dogs and dogs with gastrointestinal disease.

Gut peptide changes in patients with obstructive jaundice undergoing biliary drainage: A prospective case control study.

BACKGROUNDBiliary obstruction is a relatively common condition that affects approximately 5 in 1000 people annually. Malnutrition is very common in patients with biliary obstruction and since it is associated with significant morbidity and mortality, it is important to identify factors and mechanisms involved in its development.AIMTo determine the influence of obstructive jaundice on the hormones controlling appetite and nutritive status.METHODSThis was a prospective case control study performed in a tertiary center in Zagreb, Croatia. Patients with biliary obstruction undergoing internal biliary drainage from September 2012 until August 2013 were enrolled. After excluding patients who developed procedure related complications or were lost in the follow-up, out of initial 73 patients, 55 patients were included in the analysis, including 34 with benign and 21 with malignant disease. Meanwhile, 40 non-jaundiced controls were also included. Appetite, nutritional status, and serum ghrelin, cholecystokinin (CCK), interleukin 6 (IL-6), and tumor necrosis factor α (TNF-α) were determined at admission, 48 h and 28 d after internal biliary drainage. Chi square test was used for categorical variables. Continuous variables were analysed for normality by Kolmogorov–Smirnov test and relevant non-parametric (Mann-Whitney, Kruskal-Wallis, and Friedman) or parametric (t-test and analysis of variance) tests were used.RESULTSPatients with obstructive jaundice were significantly malnourished compared to controls, regardless of disease etiology. Plasma ghrelin and CCK levels were significantly higher in patients with obstructive jaundice. Serum bilirubin concentrations were negatively correlated with ghrelin levels and positively correlated with TNF-α, but had no correlation with CCK concentrations. After internal biliary drainage, a significant improvement of nutritional status was observed although serum concentrations of ghrelin, IL-6, and TNF-α remained significantly elevated even 28 d after the procedure. CCK levels in patients without malnutrition remained elevated 28 d after the procedure, but in patients with malnutrition, CCK levels decreased to levels comparable with those in the control group. We have not established any correlation between appetite and serum levels of ghrelin, CCK, IL-6, and TNF-α before and after biliary drainage.CONCLUSIONPossible abnormalities in ghrelin and CCK regulation may be associated with the development of malnutrition during the inflammatory response in patients with biliary obstruction.

Gastric Mobility and Gastrointestinal Hormones in Older Patients with Sarcopenia.

Sarcopenia has serious clinical consequences and poses a major threat to older people. Gastrointestinal environmental factors are believed to be the main cause. The aim of this study was to describe the relationship between sarcopenia and gastric mobility and to investigate the relationship between sarcopenia and the concentration of gastrointestinal hormones in older patients. Patients aged ≥ 75 years were recruited for this prospective study from August 2018 to February 2019 at the emergency department. The enrolled patients were tested for sarcopenia. Gastric emptying scintigraphy was conducted, and laboratory tests for cholecystokinin(CCK), glucagon-like peptide-1 (GLP-1), peptide YY (PYY), nesfatin, and ghrelin were performed during the fasting period. We enrolled 52 patients with mean age of 86.9 years, including 17 (32.7%) patients in the non-sarcopenia group, 17 (32.7%) patients in the pre-sarcopenia group, and 18 (34.6%) in the sarcopenia group. The mean gastric emptying half-time had no significant difference among three groups. The sarcopenia group had significantly higher fasting plasma concentrations of CCK, GLP-1, and PYY. We concluded that the older people with sarcopenia had significantly higher plasma concentrations of CCK, GLP-1, and PYY. In the elderly population, anorexigenic gastrointestinal hormones might have more important relationships with sarcopenia than orexigenic gastrointestinal hormones.

Understanding Fish Larvae’s Feeding Biology to Improve Aquaculture Feeding Protocols

Knowing that food ingestion and digestion are processes under neuroendocrine regulation, it is important to understand how fish larvae regulate these processes, when the digestive system itself is under development. This study aimed to analyze how gilthead seabream (Sparus aurata) larval feeding incidence and intensity were affected by time, light, and water temperature, through the analysis of gut content and how this affected cholecystokinin (CCK) content. Three short-term experiments were done: (A) 27 and 42 days post-hatch (DPH) larvae were analyzed at different intervals for 80 min, after feeding; (B) 38 and 48 DPH larvae were kept under different light intensities (0, 400, 1000 lux) for 30 min; (C) 41 DPH larvae were kept at 17, 19, 25 °C for 30 min. Feeding incidence below 100% was observed for 27 DPH larvae, and for 38 DPH larvae fed at 0 lux. Feeding intensity was several fold higher at older ages. However, the number of prey in the gut was lower at 0 lux, and higher at 25 °C. Overall, no clear pattern was observed for CCK, but at older ages increasing gut content resulted in higher CCK content. In conclusion, until 38 DPH light is important for gilthead sea bream larval feeding ability, and maturing functionality of CCK was only observed at later stages.

RETRACTED ARTICLE: Dihydroartemisinin targets fibroblast growth factor receptor 1 (FGFR1) to inhibit interleukin 17A (IL-17A)-induced hyperproliferation and inflammation of keratinocytes

Statement of Retraction Baojiang Chen, Chen Li, Guizheng Chang, and Huan Wang- 2022, Dihydroartemisinin targets fibroblast growth factor receptor 1 (FGFR1) to inhibit interleukin 17A (IL-17A)-induced hyperproliferation and inflammation of keratinocytes, Bioengineered 13(1), doi: 10.1080/21655979.2021.2021701. Since publication, significant concerns have been raised about the integrity of the data and reported results in the article. When approached for an explanation, the authors did not provide their original data or any necessary supporting information. As verifying the validity of published work is core to the integrity of the scholarly record, we are therefore retracting the article. All authors listed in this publication have been informed. We have been informed in our decision-making by our editorial policies and the COPE guidelines. The retracted article will remain online to maintain the scholarly record, but it will be digitally watermarked on each page as ‘Retracted’.

Vagal afferent cholecystokinin receptor activation is required for glucagon-like peptide-1-induced satiation.

Peripheral glucagon-like peptide-1 (GLP-1) and cholecystokinin (CCK) are secreted from enteroendocrine cells, and their plasma concentrations increase in response to eating. While the satiating effect of gut-derived CCK on food-intake control is well documented, the effect of peripheral GLP-1 is less clear. There is evidence that native GLP-1 can inhibit food intake only in the fed state but not in the fasting state. We therefore hypothesized that other gut peptides released during a meal might influence the subsequent effect of endogenous GLP-1 and investigated whether CCK could do so. We found that intraperitoneal injection of CCK in food-restricted mice inhibited food intake during the first 30-minute segment of a 1-hour session of ad libitum chow intake and that mice compensated by increasing their intake during the second half of the session. Importantly, this compensatory behaviour was abolished by an intraperitoneal injection of GLP-1 administered following an intraperitoneal injection of CCK and prior to the 1-hour session. In vivo activation of the free fatty acid 1 (FFA1) receptor with orally administered TAK875 increased plasma CCK concentration and, consistent with the effect of exogenous CCK, we found that prior oral administration of TAK875 increased the eating inhibitory effect of peripherally administered GLP-1. To examine the role of the vagus nerve in this effect, we utilized a saporin-based lesioning procedure to selectively ablate the CCK receptor-expressing gastrointestinal vagal afferent neurones (VANs). We found that the combined anorectic effect of TAK875 and GLP-1 was significantly attenuated in the absence of CCK receptor expressing VANs. Taken together, our results indicate that endogenous CCK interacts with GLP-1 to promote satiation and that activation of the FFA1 receptor can initiate this interaction by stimulating the release of CCK.

Suppression of Energy Intake by Intragastric l-Tryptophan in Lean and Obese Men: Relations with Appetite Perceptions and Circulating Cholecystokinin and Tryptophan

Backgroundl-Tryptophan reduces energy intake in healthy men. The underlying mechanisms, including appetite, plasma cholecystokinin (CCK), tryptophan (Trp), and the ratio of Trp to large neutral amino acids (Trp:LNAAs ratio), and whether responses differ in lean and obese individuals, are uncertain. ObjectivesWe evaluated the effects of intragastric Trp on energy intake (primary outcome) and their potential mechanisms, pre- and postmeal, in lean men and those with obesity. MethodsTwelve lean men [mean ± SD age: 30 ± 3 y; BMI (in kg/m2): 23 ± 1] and 13 men with obesity (mean ± SD age: 31 ± 3 y; BMI: 33 ± 1) received, on 3 separate occasions, in double-blind, randomized order, 3 g (“Trp-3”) or 1.5 g (“Trp-1.5”) Trp, or control (“C”), intragastrically, 30 min before a buffet-meal. Energy intake from the buffet-meal, hunger, fullness, and plasma CCK and amino acid concentrations were measured in response to Trp alone and for 2 h postmeal. Data were analyzed using maximum likelihood mixed-effects models, with treatment, group, and treatment-by-group interaction as fixed effects. ResultsTrp alone increased plasma CCK, Trp, and the Trp:LNAAs ratio (all P < 0.001), with no difference between groups. Trp suppressed energy intake (P < 0.001), with no difference between groups (lean, C: 1085 ± 102 kcal, Trp-1.5: 1009 ± 92 kcal, Trp-3: 868 ± 104 kcal; obese, C: 1249 ± 98 kcal, Trp-1.5: 1217 ± 90 kcal, Trp-3: 1012 ± 100 kcal). Postmeal, fullness was greater after Trp-3 than after C and Trp-1.5 (all P < 0.05), and in men with obesity than in lean men (P < 0.05). Plasma Trp and the Trp:LNAAs ratio were greater after Trp-3 and Trp-1.5 than after C (all P < 0.001), and tended to be less in men with obesity than in the lean (P = 0.07) (Trp:LNAAs ratio: lean, C: 1.5 ± 0.2, Trp-1.5: 6.9 ± 0.7, Trp-3: 10.7 ± 1.4; obese, C: 1.4 ± 0.1, Trp-1.5: 4.6 ± 0.7, Trp-3: 7.8 ± 1.3). There were inverse correlations of energy intake with plasma Trp and the Trp:LNAAs ratio in both groups (lean, both r = −0.50, P < 0.01; obese, both r = −0.40, P < 0.05). ConclusionsIntragastric Trp has potent energy intake–suppressant effects, in both lean men and those with obesity, apparently related to the Trp:LNAAs ratio.