Role of adipokines in regulation of colonic motor activity in overweight and obese individuals

The increasing proportion of the population suffering from overweight or obesity is now taking on the character of a pandemic. In the literature, there have begun to appear reports of associations in individuals with impaired colonic motility and a body mass index above 25 kg/m2. The present publication was prepared to systematize data on possible mechanisms of colonic motility disorders in overweight and obese individuals, including through changes in adipokine secretion and function. The literature search was performed in Embase, PubMed, and Google Scholar, using the key words ‘colon motility regulation’, ‘adipokines’, ‘gastrointestinal hormones’, ‘intestinal microbiota’, ‘overweight’, ‘obesity’, ‘visceral fat’.

Circulating Blood miR-155 and miR-21 Promote the Development of Acute Pancreatitis and Can Be Used to Assess the Risk Stratification of Pancreatitis

To explore the role of circulating blood miR-155 and miR-21 in promoting acute pancreatitis (AP) and evaluating the risk stratification of pancreatitis. In this experiment, 70 patients with AP treated in our hospital from October 2019 to December 2020 were included in the research group (RG), and the blood of 52 healthy cases was collected and they were included in the control group (CG). The expression of miR-155 and miR-21 in circulating blood was observed in the two groups. The diagnostic efficacy of miR-155 and miR-21 in AP was observed. The risk factors of patients with AP were observed. The expression of serum gastrointestinal hormones was observed in the two groups. The GAS and VIP in RG were higher than those in CG, while MTL and CCK were lower than those in CG. Moreover, the detection level of mild, moderate, severe, and critical patients was also significantly different ( P < 0.05 ). The expression of miR-155 and miR-21 in circulating blood of RG was significantly lower than that of CG ( P < 0.05 ), and the area under the miR-155 curve was 0.775 and the area under the miR-21 curve was 0.832. Alcoholism, GAS, VIP, MTL, CCK, miR-155, and miR-21 were the risk factors of patients. miR-155 and miR-21 show low expression in the serum of patients. The lower the expression, the more serious the disease. They are closely related to the development of AP. miR-155 and miR-21 have good diagnostic efficacy by ROC analysis, and they are expected to become effective indicators for the diagnosis and treatment of AP in the future.

Timing of Meals and Exercise Affects Hormonal Control of Glucoregulation, Insulin Resistance, Substrate Metabolism, and Gastrointestinal Hormones, but Has Little Effect on Appetite in Postmenopausal Women

The current prevalence of obesity in the US is strongly associated with excessive food intake and insufficient physical activity. This study examined whether changing the timing of exercise before or after two daily meals could alter human appetite for food. Fifty-four healthy postmenopausal women were matched by body weight and assigned to two groups: (1) two bouts of 2-h moderate-intensity exercise ending one hour before each weight-maintenance meal (XM, n = 23), (2) two-hour moderate-intensity exercise starting 1 h after each weight-maintenance meal (MX, n = 23), and one sedentary control (SED) arm (n = 8). Measurements included appetite ratings, circulating glucose, free fatty acids (FFAs), a ketone body D-ß-hydroxybutyrate (BHB), glucoregulatory hormones insulin and glucagon, and gastrointestinal hormones associated with food digestion and absorption and implicated in appetite sensations. XM group increased concentrations of FFAs and BHB during exercise and increased insulin and homeostatic assessment of insulin resistance (HOMA-IR) during postprandial periods. MX group reduced postprandial insulin and HOMA-IR by about 50% without a major change in plasma glucose. There was brief suppression of hunger and an increase in satiation in both exercise groups near the end of the first postprandial period. The time course of hunger was unrelated to the perturbations in fuel metabolism, depletion of liver glycogen, and not correlated with concentration changes in hunger-stimulating hormone ghrelin during XM exercise before meals. Similarly, there was no correlation between the time course of fullness during exercise after meals with the postprandial secretion of gastrointestinal hormones including cholecystokinin (CCK) that has been linked to satiation. Hunger and satiation appear to depend on oral intake and gastrointestinal processing of nutrients and are not affected by metabolic and hormonal consequences of the timing of exercise with respect to meals. Moderate-intensity exercise performed shortly after meals induces a rapid and highly effective lowering of insulin resistance.

Novel Effects of the Gastrointestinal Hormone Secretin on Cardiac Metabolism and Renal Function

The cardiac benefits of gastrointestinal hormones have been of interest in recent years. The aim of this study was to explore the myocardial and renal effects of the gastrointestinal hormone secretin in the GUTBAT trial (NCT03290846). A placebo-controlled crossover study was conducted on 15 healthy males in fasting conditions, where subjects were blinded to the intervention. Myocardial glucose uptake was measured with [18F]2-fluoro-2-deoxy-D-glucose ([18F]FDG) positron emission tomography. Kidney function was measured with [18F]FDG renal clearance and estimated glomerular filtration rate (eGFR). Secretin increased myocardial glucose uptake compared to placebo (secretin vs. placebo, mean + standard deviation, 15.5 + 7.4 vs. 9.7 + 4.9 μmol/100g/min, 95% confidence interval (CI) [2.2, 9.4], p=0.004). Secretin also increased [18F]FDG renal clearance (44.5 + 5.4 vs. 39.5 + 8.5 ml/min, 95%CI[1.9, 8.1], p=0.004) and eGFR was significantly increased from baseline after secretin, compared to placebo (17.8 + 9.8 vs. 6.0 + 5.2 Δml/min/1.73m2, 95%CI[6.0, 17.6], p=0.001). Our results implicate that secretin increases heart work and renal filtration, making it an interesting drug candidate for future studies in heart and kidney failure.

Hemp and buckwheat are valuable sources of dietary amino acids, beneficially modulating gastrointestinal hormones and promoting satiety in healthy volunteers

Purpose This study evaluated the postprandial effects following consumption of buckwheat, fava bean, pea, hemp and lupin compared to meat (beef); focussing on biomarkers of satiety, gut hormones, aminoacids and plant metabolites bioavailability and metabolism. Methods Ten subjects (n = 3 men; n = 7 women; 42 ± 11.8 years of age; BMI 26 ± 5.8 kg/m2) participated in six 1-day independent acute interventions, each meal containing 30 g of protein from buckwheat, fava bean, pea, hemp, lupin and meat (beef). Blood samples were collected during 24-h and VAS questionnaires over 5-h. Results Volunteers consumed significantly higher amounts of most amino acids from the meat meal, and with few exceptions, postprandial composition of plasma amino acids was not significantly different after consuming the plant-based meals. Buckwheat meal was the most satious (300 min hunger scores, p < 0.05).Significant increase in GLP-1 plasma (AUC, iAUC p = 0.01) found after hemp compared with the other plant-based meals. Decreased plasma ghrelin concentrations (iAUC p < 0.05) found on plant (hemp) vs. meat meal. Several plasma metabolites after hemp meal consumption were associated with hormone trends (partial least squares-discriminant analysis (PLS-DA): 4-hydroxyphenylpyruvic acid, indole 3-pyruvic acid, 5-hydoxytryptophan, genistein and biochanin A with GLP-1, PYY and insulin; 3-hydroxymandelic acid and luteolidin with GLP-1 and ghrelin and 4-hydroxymandelic acid, benzoic acid and secoisolariciresinol with insulin and ghrelin. Plasma branched-chain amino acids (BCAAs), (iAUC, p < 0.001); and phenylalanine and tyrosine (iAUC, p < 0.05) were lower after buckwheat comparison with meat meal. Conclusion Plants are valuable sources of amino acids which are promoting satiety. The impact of hemp and buckwheat on GLP-1 and, respectively, BCAAs should be explored further as could be relevant for aid and prevention of chronic diseases such as type 2 diabetes. Study registered with clinicaltrial.gov on 12th July 2013, study ID number: NCT01898351.

Novel Non-invasive Approaches to the Treatment of Obesity: From Pharmacotherapy to Gene Therapy

Recent insights into the pathophysiologic underlying mechanisms of obesity have led to the discovery of several promising drug targets and novel therapeutic strategies to address the global obesity epidemic and its comorbidities. Current pharmacologic options for obesity management are largely limited in number and of modest efficacy/safety profile. Therefore, the need for safe and more efficacious new agents is urgent. Drugs which are currently under investigation modulate targets across a broad range of systems and tissues, including the central nervous system, gastrointestinal hormones, adipose tissue, kidney, liver, and skeletal muscle. Beyond pharmacotherapeutics, other potential antiobesity strategies are being explored, including novel drug delivery systems, vaccines, modulation of the gut microbiome, and gene therapy. The present review summarizes the pathophysiology of energy homeostasis, and highlights pathways being explored in the effort to develop novel antiobesity medications and interventions but does not cover devices and bariatric methods. Emerging pharmacologic agents and alternative approaches targeting these pathways and relevant research in both animals and humans are presented in detail. Special emphasis is given to treatment options at the end of the development pipeline and closer to the clinic, i.e., compounds that have a higher chance to be added to our therapeutic armamentarium in the near future. Ultimately, advancements in our understanding of the pathophysiology and interindividual variation of obesity may lead to multimodal and personalized approaches to obesity treatment that will result in safe, effective and sustainable weight loss until the root causes of the problem are identified and addressed.

GASTRIN IN SERUM AND MORPHOLOGICAL STATE OF GASTRIN-SECRETING CELLS IN PATIENTS WITH GASTRIC POLYPOSIS

Objective. Numerous studies regarding gastric hormones and their regulation have been performed until now. However, the effect of the hormones on the formation and malignisation of gastric polyps still remains not clear. Our aim was to identify the relation between the level of gastrin in the blood, gastric mucosa, polyp tissue, gastric juice and pathogenesis of gastric polyposis. Materials and methods. A thorough investigation of gastrointestinal hormones in serum and gastric juice, in polyp’s tissue and mucosa, gastrin-secreting cells and proteolytic activity of gastric juice was carried out in 40 patients with gastric polyps. These patients were divided into groups, depending on the location, number, and malignancy of the polyps. As a control group, 10 healthy individuals were used to determine the normal values of the studied indicators. Results: A significant increase (more than two times) in the gastrinemia level before the surgery was noted in patients with polyp recurrence, and gastrin level increased to more significant digits of 227.0+37.4 pg/ml (p<0.05) in one year after polypectomy. Conclusion. Gastrin is apparently involved in the process of polyp formation since polyp’s growth is accompanied by elevation of serum gastrin. This is confirmed by a response of gastrin in the blood to a test meal in individuals with different duration of the disease: a marked increase in gastrinemia appears in patients suffering from gastric polyposis for more than three years. Therefore, evaluation of gastrin level in the patients’ blood can be used to predict a recurrence potential of polyps. This is evidenced by more pronounced hypergastrinemia before polypectomy in patients who had a further recurrence of the disease within one year after the surgery

Gastrointestinal hormones and β-cell function after gastric bypass and sleeve gastrectomy: an RCT (Oseberg)

Context Whether Roux-en-Y gastric bypass (RYGB) and sleeve gastrectomy (SG) differentially affect postprandial gastrointestinal hormones and β-cell function in type 2 diabetes remains unclear. Objective To compare gastrointestinal hormones and β-cell function assessed by an oral glucose tolerance test (OGTT) 5 weeks and 1 year after surgery hypothesizing higher GLP-1 levels and greater β-cell response to glucose after RYGB than after SG. Design, Setting, Patients, and Interventions Randomized, triple blind, single-center trial at a tertiary care center in Norway. Primary outcomes; diabetes remission and IVGTT derived β-cell function. Participants with obesity and type 2 diabetes allocated (1:1) to RYGB or SG. Main outcome measures Gastrointestinal hormone profiles and insulin secretion [β-cell glucose sensitivity (β-GS)] derived from 180 minutes OGTTs. Results 106 patients (67% women), mean (SD) age 48 (10) years. Diabetes remission rates at 1-year were higher after RYGB than after SG, 77% versus 48%, p = 0.002. Incremental area under the curve (iAUC0-180) glucagon-like peptide-1 (GLP-1) and β-GS increased more after RYGB than after SG, 1-year between-group difference 1173 pmol/l*min (95% CI 569 to 1776), p = 0.0010, and 0.45 pmol/kg/min/mmol (95% CI 0.15 to 0.75), p = 0.0032, respectively. Post-surgery, fasting and postprandial ghrelin levels were higher and decremental AUC0-180 ghrelin, iAUC0-180 glucose-dependent insulinotropic polypeptide, and iAUC0-60 glucagon were greater after RYGB than after SG. Diabetes remission at 1 year was associated with higher β-GS and higher GLP-1 secretion. Conclusions RYGB was associated with greater improvement in β-cell function and higher postprandial GLP-1 levels than SG.

Effects of sleeve gastrectomy on bone mass, microstructure of femurs and bone metabolism associated serum factors in obese rats

Background Sleeve gastrectomy (SG) is a profoundly effective operation for severe obese patients, but is closely associated with bone mass loss. Previous studies have reported changes of various serum factors which may be associated with bone mass loss after SG. However, those results are contradictory. In this study, we assessed the effects of SG on bone mass, microstructure of femurs, and changes in bone turnover markers (BTMs), serum adipokines, inflammatory factors and gastrointestinal hormones after SG in high-fat diet (HFD) induced obese rats. Methods Eight-week-old male Sprague–Dawley (SD) rats were fed with HFD to induce obesity. Then, SG and sham surgery were performed in anesthetized obese rats. SD rats in control group were fed with standard chow. Microstructure of femurs was scanned and analyzed by micro-computed tomography in control group, HFD sham group and HFD SG group. Serum inflammatory factors, adipokines markers, gastrointestinal hormones and BTMs were also measured. Results Bone mineral density (BMD) of trabecular bone in both HFD sham group and HFD SG group were remarkably decreased compared with control group. All serum BTMs were significantly higher in HFD SG group than HFD sham group. In the meantime, serum levels of several important inflammatory factors, gastrointestinal hormones and adipokines such as tumor necrosis factor-α (TNF-α), interleukin (IL)-6, monocyte chemoattractant protein-1(MCP-1), ghrelin, insulin and leptin in HFD SG group were remarkably reduced compared with HFD sham group, whereas glucagon-like peptide-1 (GLP-1), adiponectin, fibroblast growth factor (FGF)-19 and FGF-21 were dramatically increased after SG. Protein tyrosine phosphatase 1B (PTP1B) was significantly increased in the HFD sham group than control group. Spearman’s correlation analysis indicated that serum osteocalcin (OC) and 25-hydroxy vitamin D3 (25(OH)D3) were positively correlated with BMD of trabecular bone, whereas serum PTP1B and TNF-α were negatively related to BMD of trabecular bone. Conclusions SG aggravates bone mass loss and activates bone remodeling in obese rats. Levels of BTMs, adipokines, inflammatory factors, and gastrointestinal hormones could be affected by SG in obese rats. Serum PTP1B level might be associated with abnormal bone mass in obese rats.

Ghrelin Response to Acute and Chronic Exercise: Insights and Implications from a Systematic Review of the Literature

Background Ghrelin is a peptide hormone predominantly produced by the stomach. It exerts a wide range of functions including stimulating growth hormone release and regulating appetite, food intake, and glucose and lipid metabolism. Since physical exercise affects all these aspects, a particular interest is accorded to the relationship between ghrelin and exercise. This systematic review aimed to summarize the current available data on the topic for a better understanding of the relationship. Methods An extensive computerized search was performed in the PubMed and SPORTDiscus databases for retrieving relevant articles. The search contained the following keywords: ghrelin, appetite-related peptides, gastrointestinal peptides, gastrointestinal hormones, exercise, acute exercise, chronic exercise, training, and physical activity. Studies investigating the effects of acute/chronic exercise on circulating forms of ghrelin were included. Results The initial search identified 840 articles. After screening, 80 articles were included. Despite a heterogeneity of studies and a variability of the findings, the review suggests that acute exercise suppresses acyl ghrelin production regardless of the participants and the exercise characteristics. Long- and very long-term exercise training programs mostly resulted in increased total and des-acyl ghrelin production. The increase is more noticeable in overweight/obese individuals, and is most likely due to weight loss resulting from the training program. Conclusion The review suggests that exercise may impact ghrelin production. While the precise mechanisms are unclear, the effects are likely due to blood flow redistribution and weight loss for acute and chronic exercise, respectively. These changes are expected to be metabolically beneficial. Further research is needed for a better understanding of the relationship between ghrelin and exercise.