[Clinical effect of acupuncture for gastroesophageal reflux disease based on the "heart-stomach connection" theory and its effects on serum gastrointestinal hormones].

OBJECTIVE: To observe the effect of acupuncture on gastroesophageal reflux disease (GERD) based on the "heart-stomach connection" theory, and to explore its possible mechanisms. METHODS: Seventy patients with GERD were randomly divided into an acupuncture group (35 cases, 2 cases dropped out) and a medication group (35 cases, 1 case dropped out). The patients in the acupuncture group received acupuncture at bilateral Shenmen (HT 7), Neiguan (PC 6), Burong (ST 19), Tianshu (ST 25), Zusanli (ST 36), Gongsun (SP 4), and Zhongwan (CV 12), with needles retained for 30 min, every other day, three times a week. The patients in the medication group were treated with oral omeprazole capsules, once daily, 20 mg each time. Both groups were treated for 8 weeks. Before and after treatment, the GERD questionnaire (GERDQ), GERD-quality of life scale (GERD-QOL), Hamilton depression scale-24 (HAMD-24), Zung self-rating depression scale (SDS), and Zung self-rating anxiety scale (SAS) scores were observed. Serum levels of gastrointestinal hormones (gastrin [GAS], motilin [MTL], and vasoactive intestinal peptide [VIP]) were measured, and the clinical efficacy of both groups was evaluated. Correlation between pre-treatment GERDQ score and GERD-QOL score, HAMD-24 score, SDS score, and SAS score was analyzed. RESULTS: After treatment, the scores of GERDQ, HAMD-24, SDS, and SAS were decreased (P<0.001) and the scores of GERD-QOL were increased (P<0.001), serum levels of GAS and MTL were increased (P<0.001) in both groups, while the serum level of VIP in the acupuncture group was decreased (P<0.001) compared with those before treatment. The acupuncture group had higher GERD-QOL score and lower SAS score than the medication group (P<0.05), with lower serum VIP level (P<0.05). The total effective rate was 75.8% (25/33) in the acupuncture group, and 76.5% (26/34) in the medication group, with no significant difference between the two groups (P>0.05). GERDQ score was negatively correlated with GERD-QOL scores (r =-0.762, P<0.01) and positively correlated with HAMD-24 score, SDS score, and SAS score (r =0.709, 0.649, 0.689, P<0.01) before treatment. CONCLUSION: Based on the "heart-stomach connection" theory, acupuncture could effectively improve clinical symptoms, quality of life, and negative emotions in patients with GERD. Its mechanism may be related to the regulation of gastrointestinal hormone levels, thereby promoting the contraction of the lower esophageal sphincter.

Appetite, food intake, and gut hormone responses to glycomacropeptide protein ingestion in older adults: A feasibility, acceptability, and pilot study.

Glycomacropeptide (GMP) has a unique amino acid profile which may make less satiating than other dietary proteins. This study assessed the feasibility and likely acceptability of a leucine-enriched GMP drink and determined appetite response in older adults (OA). Thirteen OA (11f; 70 ± 4 years) were recruited for sensory assessments of a leucine-enriched GMP drink when mixed with water and with fruit smoothie, compared with whey protein isolate (WHEY). Participants also partook in a single focus group exploring acceptability to protein and supplementation. Separately, a counterbalanced, double-blind study with twelve OA (8f; 69 ± 3 years) was conducted to determine appetite and gut hormone responses. Fasting subjective appetite was recorded using visual analogue scales and a fasted venous blood sample was collected (to measures acyl-ghrelin, PYY, GLP-1, and CCK) before participants consumed either: GMP protein (27g + 3g leucine, 350 mL water), WHEY (30g, 350 mL water), or water. Participants rested for 240 min, with appetite measures and blood sampling throughout. An ad libitum pasta-based meal was then consumed. Sensory testing revealed low pleasantness rating for GMP in water vs. WHEY (16 ± 14 vs 31 ± 24, p = 0.016). GMP addition to smoothie reduced pleasantness (26 ± 21 vs. 61 ± 29, p = 0.009) and worsened the aroma (46 ± 15 vs. 69 ± 28, p = 0.014). The focus group revealed uncertainty of protein needs and a scepticism of supplements, with preference for food. Gut hormone response did not differ between GMP and WHEY (nAUC for all gut hormones p > 0.05). There was no difference between conditions for lunch ad libitum intake (549 ± 171 kcal, 512 ± 238 kcal, 460 ± 199 kcal for GMP, WHEY, and water, p = 0.175), or for subjective appetite response. Leucine-enriched GMP was not less satiating than WHEY, and low palatability and scepticism of supplements question the likely acceptability of GMP supplementation. Providing trusted nutritional advice and food enrichment/fortification may be preferred strategies for increasing protein intake in OA.

Fasting and post prandial pancreatic and enteroendocrine hormone levels in obese and non-obese participants.

Circulating insulin levels are known to be increased in people with higher body mass index (BMI) due to effects of adiposity on insulin resistance, whilst gut hormones have a more complex relationship, with fasting peptideYY (PYY) reported to be inversely related to BMI. This study aimed to further explore fasting and post prandial pancreatic and gut hormone concentrations in plasma samples from obese and non-obese participants. Participants with healthy BMI (n=15), overweight BMI (n=29) and obesity (n=161) had samples taken fasting and 30 min post mixed liquid meal for analysis of glucagon-like peptide-1 (GLP-1), PYY, glucose-dependent insulinotropic polypeptide (GIP), insulin and glucagon. Data visualiation used linear discriminant analysis for dimensionality reduction, to visualise the data and assess scaling of each hormone. Fasting levels of insulin, GIP and PYY were shown to be key classifiers between the 3 groups on ANCOVA analysis, with an observation of increased GIP levels in overweight, but not obese participants. In non-obese subjects, fasting GIP, PYY and insulin correlated with BMI, whereas in subjects with obesity only the pancreatic hormones glucagon and insulin correlated with BMI. Concentrations of total GLP-1 in the fasting state correlated strongly with glucagon levels, highlighting potential assay cross-reactivities. The study, which included a relatively large number of subjects with severe obesity, supported previous evidence of BMI correlating negatively with fasting PYY and positively with fasting insulin. The observation of increased fasting GIP levels in overweight but not obese participants deserves further validation and mechanistic investigation.

Differential Diagnosis of Post Pancreatitis Diabetes Mellitus Based on Pancreatic and Gut Hormone Characteristics.

CONTEXT: Distinguishing different types of diabetes is important in directing optimized treatment strategies and correlated epidemiological studies. OBJECTIVE: Through detailed analysis of hormone responses to mixed meal tolerance test (MMTT), we aimed to find representing characteristics of post-acute pancreatitis diabetes mellitus (PPDM-A) and post-chronic pancreatitis diabetes mellitus (PPDM-C). METHODS: Participants with PPDM-A, PPDM-C, type 1 diabetes, type 2 diabetes, and normal controls (NCs) underwent MMTT. Fasting and postprandial responses of serum glucose, C-peptide, insulin, glucagon, pancreatic polypeptide (PP), ghrelin, gastric inhibitory peptide (GIP), glucagon like peptide-1 (GLP-1), and peptide YY (PYY) were detected and compared among different groups. Focused analysis on calculated insulin sensitivity and secretion indices were performed to determine major causes of hyperglycemia in different conditions. RESULTS: Participants with PPDM-A were characterized by increased C-peptide, insulin, glucagon, and PP, but decreased ghrelin, GIP, and PYY compared with NCs. Patients with PPDM-C showed secretion insufficiency of C-peptide, insulin, ghrelin, and PYY, and higher postprandial responses of glucagon and PP than NCs. In particular, both fasting and postprandial levels of ghrelin in PPDM-C were significantly lower than other diabetes groups. PYY responses in patients with PPDM-A and PPDM-C were markedly reduced. Additionally, the insulin sensitivity of PPDM-A was decreased, and the insulin secretion for PPDM-C was decreased. CONCLUSION: Along with the continuum from acute to chronic pancreatitis, the pathological mechanism of PPDM changes from insulin resistance to insulin deficiency. Insufficient PYY secretion is a promising diagnostic marker for distinguishing PPDM from type 1 and type 2 diabetes. Absent ghrelin secretion to MMTT may help identify PPDM-C.

Impaired Brain Satiety Responses After Weight Loss in Children With Obesity.

CONTEXT: Obesity interventions often result in increased motivation to eat. OBJECTIVE: We investigated relationships between obesity outcomes and changes in brain activation by visual food cues and hormone levels in response to obesity intervention by family-based behavioral treatment (FBT). METHODS: Neuroimaging and hormone assessments were conducted before and after 24-week FBT intervention in children with obesity (OB, n = 28), or children of healthy weight without intervention (HW, n = 17), all 9- to 11-year-old boys and girls. We evaluated meal-induced changes in neural activation to high- vs low-calorie food cues across appetite-processing brain regions and gut hormones. RESULTS: Among children with OB who underwent FBT, greater declines of BMI z-score were associated with lesser reductions after the FBT intervention in meal-induced changes in neural activation to high- vs low-calorie food cues across appetite-processing brain regions (P < 0.05), and the slope of relationship was significantly different compared with children of HW. In children with OB, less reduction in brain responses to a meal from before to after FBT was associated with greater meal-induced reduction in ghrelin and increased meal-induced stimulation in peptide YY and glucagon-like peptide-1 (all P < 0.05). CONCLUSION: In response to FBT, adaptations of central satiety responses and peripheral satiety-regulating hormones were noted. After weight loss, changes of peripheral hormone secretion support weight loss, but there was a weaker central satiety response. The findings suggest that even when peripheral satiety responses by gut hormones are intact, the central regulation of satiety is disturbed in children with OB who significantly improve their weight status during FBT, which could favor future weight regain.

Oral lactate slows gastric emptying and suppresses appetite in young males.

BACKGROUND: Lactate serves as an alternative energy fuel but is also an important signaling metabolite. We aimed to investigate whether oral lactate administration affects appetite-regulating hormones, slows gastric emptying rate, and dampens appetite. METHODS: Ten healthy male volunteers were investigated on two separate occasions: 1) following oral ingestion of D/L-Na-lactate and 2) following oral ingestion of isotonic iso-voluminous NaCl and intravenous iso-lactemic D/L-Na-lactate infusions. Appetite was evaluated by questionnaires and ad libitum meal tests were performed at the end of each study day. Gastric emptying rate was evaluated using the acetaminophen test. RESULTS: Plasma concentrations of growth differential factor 15 (GDF15, primary outcome) increased following oral and iv administration of lactate (p < 0.001) with no detectable difference between interventions (p = 0.15). Oral lactate administration lowered plasma concentrations of acylated ghrelin (p = 0.02) and elevated glucagon like peptide-1 (GLP-1, p = 0.045), insulin (p < 0.001), and glucagon (p < 0.001) compared with iv administration. Oral lactate administration slowed gastric emptying (p < 0.001), increased the feeling of being "full" (p = 0.008) and lowered the "anticipated future food intake" (p = 0.007) compared with iv administration. Food intake during the ad libitum meal test did not differ between the two study days. CONCLUSION: Oral lactate administration has a direct effect on the upper gastrointestinal tract, affecting gut hormone secretion, motility and appetite sensations which cannot be mediated through lactate in the systemic circulation alone. These data suggest that compounds rich in lactate may be useful in the treatment of metabolic disease. CLINICAL TRIAL REGISTRY NUMBER: NCT0429981, https://clinicaltrials.gov/ct2/show/NCT04299815.

High plasma and lingual uroguanylin as potential contributors to changes in food preference after sleeve gastrectomy.

BACKGROUND: The biological mediators supporting long-term weight loss and changes in dietary choice behaviour after sleeve gastrectomy remain unclear. Guanylin and uroguanylin are gut hormones involved in the regulation of satiety, food preference and adiposity. Thus, we sought to analyze whether the guanylin system is involved in changes in food preference after sleeve gastrectomy in obesity. METHODS: Proguanylin (GUCA2A) and prouroguanylin (GUCA2B) were determined in patients with severe obesity (n = 41) as well as in rats with diet-induced obesity (n = 48), monogenic obesity (Zucker fa/fa) (n = 18) or in a food choice paradigm (normal diet vs high-fat diet) (n = 16) submitted to sleeve gastrectomy. Lingual distribution and expression of guanylins (GUCA2A and GUCA2B) and their receptor GUCY2C as well as the fatty acid receptor CD36 were evaluated in the preclinical models. RESULTS: Circulating concentrations of GUCA2A and GUCA2B were increased after sleeve gastrectomy in patients with severe obesity as well as in rats with diet-induced and monogenic (fa/fa) obesity. Interestingly, the lower dietary fat preference observed in obese rats under the food choice paradigm as well as in patients with obesity after sleeve gastrectomy were negatively associated with post-surgical GUCA2B levels. Moreover, sleeve gastrectomy upregulated the low expression of GUCA2A and GUCA2B in taste bud cells of tongues from rats with diet-induced and monogenic (fa/fa) obesity in parallel to a downregulation of the lingual lipid sensor CD36. CONCLUSIONS: The increased circulating and lingual GUCA2B after sleeve gastrectomy suggest an association between the uroguanylin-GUCY2C endocrine axis and food preference through the regulation of gustatory responses.

Serum prokineticin-2 in prepubertal and adult Klinefelter individuals.

The prokineticin-2 (PROK2) is a small peptide belonging to the prokineticin family. In humans and rodents this chemokine is primarily involved in the control of central and peripheral reproductive processes. Klinefelter's syndrome (KS) is the first cause of male genetic infertility, due to an extra X chromosome, which may occur with a classical karyotype (47, XXY) or mosaic forms (46, XY/47, XXY). In affected subjects, pubertal maturation usually begins at an adequate chronological age, but when development is almost complete, they display a primary gonadal failure, with early spermatogenesis damage, and later onset of testosterone insufficiency. Thus, the main aim of the present study was to investigate the serum levels of PROK2 in prepubertal and adult KS patients, comparing them with healthy subjects. We showed for the first time the presence of PROK2 in the children serum but with significant changes in KS individuals. Indeed, compared with healthy subjects characterized by PROK2 serum elevation during the growth, KS individuals showed constant serum levels during the sexual maturation phase (higher during the prepubertal phase but lower during the adult age). In conclusion, these data indicate that in KS individuals PROK2 may be considered a biomarker for investigating the SK infertility process.

The acute effect of fasted exercise on energy intake, energy expenditure, subjective hunger and gastrointestinal hormone release compared to fed exercise in healthy individuals: a systematic review and network meta-analysis.

OBJECTIVE: To determine the acute effect of fasted and fed exercise on energy intake, energy expenditure, subjective hunger and gastrointestinal hormone release. METHODS: CENTRAL, Embase, MEDLINE, PsycInfo, PubMed, Scopus and Web of Science databases were searched to identify randomised, crossover studies in healthy individuals that compared the following interventions: (i) fasted exercise with a standardised post-exercise meal [FastEx + Meal], (ii) fasted exercise without a standardised post-exercise meal [FastEx + NoMeal], (iii) fed exercise with a standardised post-exercise meal [FedEx + Meal], (iv) fed exercise without a standardised post-exercise meal [FedEx + NoMeal]. Studies must have measured ad libitum meal energy intake, within-lab energy intake, 24-h energy intake, energy expenditure, subjective hunger, acyl-ghrelin, peptide YY, and/or glucagon-like peptide 1. Random-effect network meta-analyses were performed for outcomes containing ≥5 studies. RESULTS: 17 published articles (23 studies) were identified. Ad libitum meal energy intake was significantly lower during FedEx + Meal compared to FedEx + NoMeal (MD: -489 kJ; 95% CI, -898 to -80 kJ; P = 0.019). Within-lab energy intake was significantly lower during FastEx + NoMeal compared to FedEx + NoMeal (MD: -1326 kJ; 95% CI, -2102 to -550 kJ; P = 0.001). Similarly, 24-h energy intake following FastEx + NoMeal was significantly lower than FedEx + NoMeal (MD: -2095 kJ; 95% CI, -3910 kJ to -280 kJ; P = 0.024). Energy expenditure was however significantly lower during FastEx + NoMeal compared to FedEx+NoMeal (MD: -0.67 kJ/min; 95% CI, -1.10 to -0.23 kJ/min; P = 0.003). Subjective hunger was significantly higher during FastEx + Meal (MD: 13 mm; 95% CI, 5-21 mm; P = 0.001) and FastEx + NoMeal (MD: 23 mm; 95% CI, 16-30 mm; P < 0.001) compared to FedEx + NoMeal. CONCLUSION: FastEx + NoMeal appears to be the most effective strategy to produce a short-term decrease in energy intake, but also results in increased hunger and lowered energy expenditure. Concerns regarding experimental design however lower the confidence in these findings, necessitating future research to rectify these issues when investigating exercise meal timing and energy balance. PROSPERO REGISTRATION NUMBER: CRD42020208041. KEY POINTS: Fed exercise with a standardised post-exercise meal resulted in the lowest energy intake at the ad libitum meal served following exercise completion. Fasted exercise without a standardised post-exercise meal resulted in the lowest within-lab and 24-h energy intake, but also produced the lowest energy expenditure and highest hunger. Methodological issues lower the confidence in these findings and necessitate future work to address identified problems.

Gastrointestinal Hormones in Healthy Adults: Reliability of Repeated Assessments and Interrelations with Eating Habits and Physical Activity.

Background: Gastrointestinal hormones (GIHs) are crucial for the regulation of a variety of physiological functions and have been linked to hunger, satiety, and appetite control. Thus, they might constitute meaningful biomarkers in longitudinal and interventional studies on eating behavior and body weight control. However, little is known about the physiological levels of GIHs, their intra-individual stability over time, and their interaction with other metabolic and lifestyle-related parameters. Therefore, the aim of this pilot study is to investigate the intra-individual stability of GIHs in normal-weight adults over time. Methods: Plasma concentrations of ghrelin, leptin, GLP-1 (glucagon-like-peptide), and PP (pancreatic polypeptide) were assessed by enzyme-linked immunosorbent assay (ELISA) in 17 normal-weight, healthy adults in a longitudinal design at baseline and at follow-up six months later. The reliability of the measurements was estimated using intra-class correlation (ICC). In a second step, we considered the stability of GIH levels after controlling for changes in blood glucose and hemoglobin A1 (HbA1c) as well as self-reported physical activity and dietary habits. Results: We found excellent reliability for ghrelin, good reliability for GLP1 and PP, and moderate reliability for leptin. After considering glucose, HbA1c, physical activity, and dietary habits as co-variates, the reliability of ghrelin, GLP1, and PP did not change significantly; the reliability of leptin changed to poor reliability. Conclusions: The GIHs ghrelin, GLP1, and PP demonstrated good to excellent test-retest reliability in healthy individuals, a finding that was not modified after adjusting for glucose control, physical activity, or dietary habits. Leptin showed only moderate to poor reliability, which might be linked to weight fluctuations, albeit small, between baseline and follow-up assessment in our study sample. Together, these findings support that ghrelin, GLP1, and PP might be further examined as biomarkers in studies on weight control, with GLP1 and PP serving as anorexic markers and ghrelin as an orexigenic marker. Additional reliability studies in obese individuals are necessary to verify or refute our findings for this cohort.

Plasma Prokineticin 1, a prognostic biomarker in colorectal cancer patients with curative resection: a retrospective cohort study.

BACKGROUND: Prokineticin 1 (PROK1) was reported as an angiogenic factor, which is associated with tumor progression, cell invasion, and metastasis in colorectal cancer. Although the association between PROK1 expression in primary cancer lesion and patient prognosis was reported, it is unclear whether plasma PROK1 concentration may be a predictive factor in colorectal cancer patients. This study investigated the association between PROK1 concentration in plasma and prognosis in colorectal cancer patients. METHODS: We measured preoperative PROK1 plasma levels using ELISA method, while PROK1 expression in primary cancer lesion was evaluated using immunohistochemistry (IHC). The association between plasma PROK1 levels and cancer-related survival rate (CRS) was evaluated. Additionally, we examined whether simultaneous PROK1 expression in both primary cancer lesions and plasma was correlated with CRS. The cancer-related survival rate was calculated using the Kaplan-Meier method, and survival estimates were compared using the log-rank test. RESULTS: We have gathered eligible 130 CRC patients retrospectively. Out of 130 patients, 61 (46.9%) were positive on IHC in primary cancer, and 69 (53.1%) were negative, while 43 (33.1%) had high-value PROK1 in plasma. Out of these 43, 30 (25.4%) also had concomitant higher IHC expression in primary cancer. The plasma PROK1 levels tended to increase with advancing stages. The plasma PROK1-positive group had a lower 5-year CRS than the negative group (63.6% vs. 88.2%; P = 0.006). Additionally, simultaneous PROK1 expression was associated with a more significant decrease of 5-year CRS than both negative groups in all stages (76.2% vs. 92.5%; P = 0.003) and stage III (59.3% vs. 84.5%; P = 0.047). Multivariate analysis showed simultaneous PROK1 expression was independently associated with worse CRS (HR, 1.97; 95% CI 1.20­3.24, P < 0.01). CONCLUSION: PROK1 expression in preoperative plasma reflects poor prognosis in patients undergoing curative resection for colorectal cancer. The plasma PROK1 level may be a potential predictive marker, especially in stage III colorectal cancer patients.

Associations between Postprandial Gut Hormones and Markers of Bone Remodeling.

Gut-derived hormones have been suggested to play a role in bone homeostasis following food intake, although the associations are highly complex and not fully understood. In a randomized, two-day cross-over study on 14 healthy individuals, we performed postprandial time-course studies to examine the associations of the bone remodeling markers carboxyl-terminal collagen type I crosslinks (CTX) and procollagen type 1 N-terminal propeptide (P1NP) with the gut hormones glucose-dependent insulinotropic polypeptide (GIP), glucagon-like peptide 1 (GLP-1), and peptide YY (PYY) using two different meal types-a standardized mixed meal (498 kcal) or a granola bar (260 kcal). Plasma concentrations of total GIP, total GLP-1, total PYY, CTX, and P1NP were measured up to 240 min after meal intake, and the incremental area under the curve (iAUC) for each marker was calculated. The iAUC of CTX and P1NP were used to assess associations with the iAUC of GIP, GLP-1, and PYY in linear mixed effect models adjusted for meal type. CTX was positively associated with GIP and GLP-1, and it was inversely associated with PYY (all p < 0.001). No associations of P1NP with GIP or GLP-1 and PYY were found. In conclusion, the postprandial responses of the gut hormones GIP, GLP-1, and PYY are associated with the bone resorption marker CTX, supporting a link between gut hormones and bone homeostasis following food intake.

Deoxynivalenol (Vomitoxin)-Induced Anorexia Is Induced by the Release of Intestinal Hormones in Mice.

Deoxynivalenol (DON), also known as vomitoxin, is a mycotoxin that can cause antifeeding and vomiting in animals. However, the mechanism of DON inducing anorexia is complicated. Studies have shown that intestinal hormones play a significant part in the anorexia caused by DON. We adopted the "modeling of acute antifeeding in mice" as the basic experimental model, and used two methods of gavage and intraperitoneal injection to explore the effect of intestinal hormones on the antifeedant response induced by DON in mice. We found that 1 and 2.5 mg/kg·bw of DON can acutely induce anorexia and increase the plasma intestinal hormones CCK, PYY, GIP, and GLP-1 in mice within 3 h. Direct injection of exogenous intestinal hormones CCK, PYY, GIP, and GLP-1 can trigger anorexia behavior in mice. Furthermore, the PYY receptor antagonist JNJ-31020028, GLP-1 receptor antagonist Exendin(9-39), CCK receptor antagonist Proglumide, GIP receptor antagonist GIP(3-30)NH2 attenuated both intestinal hormone and DON-induced anorectic responses. These results indicate that intestinal hormones play a critical role in the anorexia response induced by DON.

The incessant increase curve during oral glucose tolerance tests in Chinese adults with type 2 diabetes and its association with gut hormone levels.

Glucose curve shapes during oral glucose tolerance tests (OGTTs) are mainly classified as incessant increase, monophasic and biphasic. Youth with an incessant increase curve have worse ß-cell function. The aim of this paper was to investigate the incessant increase curve in Chinese adults with type 2 diabetes (T2DM), and its association with ß-cell function and gut hormone levels. Eighty-nine Chinese patients (59 males and 30 females) were included in this study with a mean age of 50.56 ±â€¯16.00 years. They were all recently diagnosed with T2DM and underwent 180-min OGTTs. Data on demographics, ß-cell function, and insulin sensitivity were also collected. Gut hormones, including glucagon-like peptide-1 (GLP-1), glucose-dependent insulinotropic polypeptide (GIP), and ghrelin, were also detected during the OGTT. A total of 39.3 % of subjects had an incessant increase in the glucose response curve, while 59.6 % had a monophasic curve. Because only one curve was classified as biphasic, patients with a biphasic curve were omitted from further research. Lower plasma C-peptide, HOMA2-ß, area under the curve (AUC) of C-peptide, and ratio of AUC of insulin to AUC of glucose were found in patients with incessant increase curves compared to those with monophasic curves (P < 0.05). Higher glycated hemoglobin (HbA1c) was found in subjects with an incessant increase curve (P < 0.05). Importantly, fasting plasma ghrelin was lower and incremental ghrelin at 120 min was higher in the incessant increase group (P < 0.05), irrespective of age, sex, body mass index (BMI), fasting glucose, and fasting insulin. Time to peak is also a parameter of the OGTT curve shape. In the late-peak group, GLP-1 at 120 min and the AUC of GLP-1 were elevated compared with those in the early-peak group (P < 0.05). In Chinese adults with T2DM, the incessant increase in OGTT shape indicated impaired insulin secretion. Lower fasting ghrelin and absence of ghrelin drops after glucose load may be associated with the incessant increase OGTT shape. In addition, compensatory elevated GLP-1 dose not prevent peak delay in the OGTT curve. Gut hormones may have an effect on OGTT shapes in T2DM adults.

Reversal of Functional Brain Activity Related to Gut Microbiome and Hormones After VSG Surgery in Patients With Obesity.

CONTEXT: Vertical sleeve gastrectomy (VSG) is becoming a prioritized surgical intervention for obese individuals; however, the brain circuits that mediate its effective control of food intake and predict surgical outcome remain largely unclear. OBJECTIVE: We investigated VSG-correlated alterations of the gut-brain axis. METHODS: In this observational cohort study, 80 patients with obesity were screened. A total of 36 patients together with 26 normal-weight subjects were enrolled and evaluated using the 21-item Three-Factor Eating Questionnaire (TFEQ), MRI scanning, plasma intestinal hormone analysis, and fecal sample sequencing. Thirty-two patients underwent VSG treatment and 19 subjects completed an average of 4-month follow-up evaluation. Data-driven regional homogeneity (ReHo) coupled with seed-based connectivity analysis were used to quantify VSG-related brain activity. Longitudinal alterations of body weight, eating behavior, brain activity, gastrointestinal hormones, and gut microbiota were detected and subjected to repeated measures correlation analysis. RESULTS: VSG induced significant functional changes in the right putamen (PUT.R) and left supplementary motor area, both of which correlated with weight loss and TFEQ scores. Moreover, postprandial levels of active glucagon-like peptide-1 (aGLP-1) and Ghrelin were associated with ReHo of PUT.R; meanwhile, relative abundance of Clostridia increased by VSG was associated with improvements in aGLP-1 secretion, PUT.R activity, and weight loss. Importantly, VSG normalized excessive functional connectivities with PUT.R, among which baseline connectivity between PUT.R and right orbitofrontal cortex was related to postoperative weight loss. CONCLUSION: VSG causes correlated alterations of gut-brain axis, including Clostridia, postprandial aGLP-1, PUT.R activity, and eating habits. Preoperative connectivity of PUT.R may represent a potential predictive marker of surgical outcome in patients with obesity.

Orosensory Perception of Fat/Sweet Stimuli and Appetite-Regulating Peptides before and after Sleeve Gastrectomy or Gastric Bypass in Adult Women with Obesity.

The aim of this study was to explore the impact of bariatric surgery on fat and sweet taste perceptions and to determine the possible correlations with gut appetite-regulating peptides and subjective food sensations. Women suffering from severe obesity (BMI > 35 kg/m2) were studied 2 weeks before and 6 months after a vertical sleeve gastrectomy (VSG, n = 32) or a Roux-en-Y gastric bypass (RYGB, n = 12). Linoleic acid (LA) and sucrose perception thresholds were determined using the three-alternative forced-choice procedure, gut hormones were assayed before and after a test meal and subjective changes in oral food sensations were self-reported using a standardized questionnaire. Despite a global positive effect of both surgeries on the reported gustatory sensations, a change in the taste sensitivity was only found after RYGB for LA. However, the fat and sweet taste perceptions were not homogenous between patients who underwent the same surgery procedure, suggesting the existence of two subgroups: patients with and without taste improvement. These gustatory changes were not correlated to the surgery-mediated modifications of the main gut appetite-regulating hormones. Collectively these data highlight the complexity of relationships between bariatric surgery and taste sensitivity and suggest that VSG and RYGB might impact the fatty taste perception differently.

Oat Polar Lipids Improve Cardiometabolic-Related Markers after Breakfast and a Subsequent Standardized Lunch: A Randomized Crossover Study in Healthy Young Adults.

It has been suggested that intake of polar lipids may beneficially modulate various metabolic variables. The purpose of this study was to evaluate the effect of oat polar lipids on postprandial and second meal glycemic regulation, blood lipids, gastrointestinal hormones, and subjective appetite-related variables in healthy humans. In a randomized design, twenty healthy subjects ingested four liquid cereal-based test beverages (42 g of available carbohydrates) containing: i. 30 g of oat oil with a low concentration (4%) of polar lipids (PLL), ii. 30 g of oat oil containing a high concentration (40%) of polar lipids (PLH), iii. 30 g of rapeseed oil (RSO), and iv. no added lipids (NL). The products were served as breakfast meals followed by a standardized lunch. Test variables were measured at fasting and during 3 h after breakfast and two additional hours following a standardized lunch. PLH reduced glucose and insulin responses after breakfast (0-120 min) compared to RSO, and after lunch (210-330 min) compared to RSO and PLL (p < 0.05). Compared to RSO, PLH resulted in increased concentrations of the gut hormones GLP-1 and PYY after the standardized lunch (p < 0.05). The results suggest that oat polar lipids have potential nutraceutical properties by modulating acute and second meal postprandial metabolic responses.

Do Gut Hormones Contribute to Weight Loss and Glycaemic Outcomes after Bariatric Surgery?

Bariatric surgery is an effective intervention for management of obesity through treating dysregulated appetite and achieving long-term weight loss maintenance. Moreover, significant changes in glucose homeostasis are observed after bariatric surgery including, in some cases, type 2 diabetes remission from the early postoperative period and postprandial hypoglycaemia. Levels of a number of gut hormones are dramatically increased from the early period after Roux-en-Y gastric bypass and sleeve gastrectomy-the two most commonly performed bariatric procedures-and they have been suggested as important mediators of the observed changes in eating behaviour and glucose homeostasis postoperatively. In this review, we summarise the current evidence from human studies on the alterations of gut hormones after bariatric surgery and their impact on clinical outcomes postoperatively. Studies which assess the role of gut hormones after bariatric surgery on food intake, hunger, satiety and glucose homeostasis through octreotide use (a non-specific inhibitor of gut hormone secretion) as well as with exendin 9-39 (a specific glucagon-like peptide-1 receptor antagonist) are reviewed. The potential use of gut hormones as biomarkers of successful outcomes of bariatric surgery is also evaluated.

Gut Hormones in Health and Obesity: The Upcoming Role of Short Chain Fatty Acids.

We are currently facing an obesity pandemic, with worldwide obesity rates having tripled since 1975. Obesity is one of the main risk factors for the development of non-communicable diseases, which are now the leading cause of death worldwide. This calls for urgent action towards understanding the underlying mechanisms behind the development of obesity as well as developing more effective treatments and interventions. Appetite is carefully regulated in humans via the interaction between the central nervous system and peripheral hormones. This involves a delicate balance in external stimuli, circulating satiating and appetite stimulating hormones, and correct functioning of neuronal signals. Any changes in this equilibrium can lead to an imbalance in energy intake versus expenditure, which often leads to overeating, and potentially weight gain resulting in overweight or obesity. Several lines of research have shown imbalances in gut hormones are found in those who are overweight or obese, which may be contributing to their condition. Therefore, this review examines the evidence for targeting gut hormones in the treatment of obesity by discussing how their dysregulation influences food intake, the potential possibility of altering the circulating levels of these hormones for treating obesity, as well as the role of short chain fatty acids and protein as novel treatments.

Effect of the Natural Sweetener Xylitol on Gut Hormone Secretion and Gastric Emptying in Humans: A Pilot Dose-Ranging Study.

Sugar consumption is associated with a whole range of negative health effects and should be reduced and the natural sweetener xylitol might be helpful in achieving this goal. The present study was conducted as a randomized, placebo-controlled, double-blind, cross-over trial. Twelve healthy, lean volunteers received intragastric solutions with 7, 17 or 35 g xylitol or tap water on four separate days. We examined effects on: gut hormones, glucose, insulin, glucagon, uric acid, lipid profile, as well as gastric emptying rates, appetite-related sensations and gastrointestinal symptoms. We found: (i) a dose-dependent stimulation of cholecystokinin (CCK), active glucagon-like peptide-1 (aGLP-1), peptide tyrosine tyrosine (PYY)-release, and decelerated gastric emptying rates, (ii) a dose-dependent increase in blood glucose and insulin, (iii) no effect on motilin, glucagon, or glucose-dependent insulinotropic peptide (GIP)-release, (iv) no effect on blood lipids, but a rise in uric acid, and (v) increased bowel sounds as only side effects. In conclusion, low doses of xylitol stimulate the secretion of gut hormones and induce a deceleration in gastric emptying rates. There is no effect on blood lipids and only little effect on plasma glucose and insulin. This combination of properties (low-glycemic sweetener which stimulates satiation hormone release) makes xylitol an attractive candidate for sugar replacement.