Gut hormones, and short bowel syndrome: The enigmatic role of glucagon-like peptide-2 in the regulation of intestinal adaptation

Short bowel syndrome （SBS） refers to the malabsorption of nutrients, water, and essential vitamins as a result of disease or surgical removal of parts of the small intestine. The most common reasons for removing part of the small intestine are due to surgical intervention for the treatment of either Crohn＇s disease or necrotizing enterocolitis. Intestinal adaptation following resection may take weeks to months to be achieved, thus nutritional support requires a variety of therapeutic measures, which include parenteral nutrition. Improper nutrition management can leave the SBS patient malnourished and/or dehydrated, which can be life threatening. The development of therapeutic strategies that reduce both the complications and medical costs associated with SBS/long-term parenteral nutrition while enhancing the intestinal adaptive response would be valuable. Currently, therapeutic options available for the treatment of SBS are limited. There are many potential stimulators of intestinal adaptation including peptide hormones, growth factors, and neuronally-derived components. Glucagon-like peptide-2 （GLP-2） is one potential treatment for gastrointestinal disorders associated with insufficient mucosal function. A significant body of evidence demonstrates that GLP-2 is atrophic hormone that plays an important role in controlling intestinal adaptation. Recent data from clinical trials demonstrate that GLP-2 is safe, well-tolerated, and promotes intestinal growth in SBS patients. However, the mechanism of action and the localization of the glucagon-like peptide-2 receptor （GLP-2R） remains an enigma. This review summarizes the role of a number of mucosal-derived factors that might be involved with intestinal adaptation processes; however, this discussion primarily examines the physiology, mechanism of action, and utility of GLP-2 in the regulation of intestinal mucosal growth.

Could the improvement of obesity-related co-morbidities depend on modified gut hormones secretion?

Obesity and its associated diseases are a worldwide epidemic disease. Usual weight loss cures- as diets, physical activity, behavior therapy and pharmacotherapy- have been continuously implemented but still have relatively poor long-term success and mainly scarce adherence. Bariatric surgery is to date the most effective long term treatment for morbid obesity and it has been proven to reduce obesity-related co-morbidities, among them nonalcoholic fatty liver disease, and mortality. This article summarizes such variations in gut hormones following the current metabolic surgery procedures. The profile of gut hormonal changes after bariatric surgery represents a strategy for the individuation of the most performing surgical procedures to achieve clinical results. About this topic, experts suggest that the individuation of the crosslink among the gut hormones, microbiome, the obesity and the bariatric surgery could lead to new and more specific therapeutic interventions for severe obesity and its co-morbidities, also non surgical.

Influence of Familiarity on Energy Intake and Plasma Gut Hormone Concentration in Lean and Overweight Young Male Students

Objective This study is to examine the influence of familiarity on energy intake, eating behavior, and concentration of the plasma gut hormones in lean and overweight young male subjects. Methods Twenty-eight lean and twenty-eight overweight participants were recruited. Their food consumption was documented and analyzed when they had a test meal while they were paired with friends or strangers at the same weight stature. Their eating behavior was recorded with cameras hidden in the carton, and postprandial plasma gut hormone concentration were measured. Results Compared with overweight strangers（OS）, overweight friends（OF） had increased food consumption, prolonged and decreased number of chews per 10 g food. Compared with OS, postprandial plasma concentration of cholecystokinin-8 was significantly lower in OF group at 30, 60, and 90 min, whereas the concentration of glucagon-like peptide 1 was significantly lower at 60 and 90 min. Plasma ghrelin concentration was significantly higher in the OF group than that in the OS group at 90 and 120 min. No significant differences in gut hormone concentration were observed between lean strangers（LS） and lean friends（LF） groups at all time points. Conclusion Familiarity plays an important role in increasing energy intake and in changing of postprandial gut hormone concentration in overweight individuals.

Bariatric surgery in patients with non-alcoholic fatty liver disease-from pathophysiology to clinical effects

Non-alcoholic fatty liver disease(NAFLD) is increasingly recognized as a significant liver disease,and it covers the disease spectrum from simple steatosis with a risk of development of non-alcoholic steatohepatitis(NASH) to fibrosis,subsequent cirrhosis,end-stage liver failure,and liver cancer with a potential need for liver transplantation.NAFLD and NASH are closely related to obesity,metabolic syndrome,and type 2 diabetes(T2 D).The role of gut hormones,especially glucagon-like peptide 1(GLP-1),is important in NAFLD.Bariatric surgery has the potential for inducing great weight loss and may improve the symptoms of metabolic syndrome and T2 D.Recent data demonstrated significant effects of bariatric surgery on GLP-1 and other gut hormones and important lipid metabolic and inflammatory abnormalities in the pathophysiology of NAFLD.Therefore,bariatric surgery may reverse the pathological liver changes in NAFLD and NASH patients.In the present review,we describe NAFLD and NASH pathophysiology and the primary effects of bariatric surgery on metabolic pathways.We performed a systematic review of the beneficial and harmful effects and focused on changes in liver disease severity in NAFLD and NASH patients.The specific focus was liver histopathology as assessed by the invasive liver biopsy.Additionally,we reviewed several non-invasive methods used for the assessment of liver disease severity following bariatric surgery.

Changes of the gastric endocrine cells in the C57BL/6 mouse after implantation of murine lung carcinoma: An immunohistochemical quantitative study

AIM: The regional distributions and relative frequencies of some gastric endocrine cells of C57BL/6 mice were studied by immunohistochemical method using seven types of specific antisera against chromogranin A (CGA), serotonin, somatostatin, gastrin, cholecystokinin (CCK)-8, glucagon and human pancreatic polypeptide (HPP) after subcutaneous implantation of murine lung carcinoma (3LL) cells. METHODS: The experimental animals were divided into two groups, one is non-implanted sham and the other is 3LL-implanted group. Samples were collected from the two regions of stomach (fundus and pylorus) at 28 d after implantation of 3LL cells (1x105 cell/mouse). RESULTS: In this study, all the seven types of immunoreactive (IR) cells were identified except for HPP. Most of these IR cells in the gastric portion were generally spherical or spindle in shape (open-type cell) while cells showing round in shape (closed-type cell) were found occasionally. The regional distributions of gastric endocrine cells in the 3LL-implanted group were similar to those of non-implanted sham. However, significant decreases of some types of IR cells were detected in 3LL-implanted group compared to those of non-implanted sham. In addition, the IR cells showing degranulation were numerously detected in 3LL-implanted group. CGA-, serotonin- and somatostatin-IR cells in the fundus and pylorus regions, and gastrin-IR cells in the pylorus regions of 3LL-implanted groups significantly decreased compared to those of non-implanted sham. However, no changes on frequencies of CCK-8- and glucagon-IR cells were demonstrated between 3LL-implanted and non-implanted groups. CONCLUSION: Endocrine cells are the anatomical units responsible for the production of gut hormones, and the change in their density would reflect a change in the capacity of producing these hormones. Implantation of tumor cell mass (3LL) induced severe quantitative changes of gastric endocrine cell density, and the abnormality in density of gastric endocrine cells may contribute to the development of gastrointestinal symptoms such as anorexia and indigestion, frequently encountered in patients with cancer.

Impact of intrarectal chromofungin treatment on dendritic cellsrelated markers in different immune compartments in colonic inflammatory conditions

BACKGROUND Chromofungin(CHR:chromogranin-A 47-66)is a chromogranin-A derived peptide with anti-inflammatory and anti-microbial properties.Ulcerative colitis(UC)is characterized by a colonic decrease of CHR and a dysregulation of dendritic CD11c+cells.AIM To investigate the association between CHR treatment and dendritic cells(DCs)-related markers in different immune compartments in colitis.METHODS A model of acute UC-like colitis using dextran sulphate sodium(DSS)was used in addition to biopsies collected from UC patients.RESULTS Intrarectal CHR treatment reduced the severity of DSS-induced colitis and was associated with a significant decrease in the expression of CD11c,CD40,CD80,CD86 and interleukin(IL)-12p40 in the inflamed colonic mucosa and CD11c,CD80,CD86 IL-6 and IL-12p40 within the mesenteric lymph nodes and the spleen.Furthermore,CHR treatment decreased CD80 and CD86 expression markers of splenic CD11c+cells and decreased NF-κB expression in the colon and of splenic CD11c+cells.In vitro,CHR decreased CD40,CD80,CD86 IL-6 and IL-12p40 expression in naïve bone marrow-derived CD11c+DCs stimulated with lipopolysaccharide.Pharmacological studies demonstrated an impact of CHR on the NF-κB pathway.In patients with active UC,CHR level was reduced and showed a negative linear relationship with CD11c and CD86.CONCLUSION CHR has protective properties against intestinal inflammation via the regulation of DC-related markers and CD11c+cells.CHR could be a potential therapy of UC.

Amino acid sensing in the gut and its mediation in gut-brain signal transduction

Animal gastrointestinal tract is not only a digestive organ, but also a nutrient sensing organ which detects luminal nutrient and thus can regulate food intake. There are many amino acid sensing receptors and transporters in the gut. Amino acids sensing by these receptors and transporters can stimulate the intestinal endocrine cells to release a variety of gut hormones. These hormones trigger a series of physiological effects via the nerve system. This review summarized the recent advance on the amino acid sensing receptors and transporters in the gastrointestinal tract, the gut hormones released from the intestinal endocrine cells and the hormones-induced signal transduction between the gut and brain. A better understanding of these processes may help to gain further insight into the specific role of amino acids in digestion and provide guidelines in developing strategy for the better use of amino acids in the diet.

Propionate stimulates the secretion of satiety hormones and reduces acute appetite in a cecal fistula pig model

Short-chain fatty acids(SCFA)can regulate appetite by stimulating the secretion of satiety hormones.However,the impact of short-chain fatty acid propionate on the release of gut satiety hormones and appetite regulation in pigs is not completely understood.In this study,16 pigs were infused with saline or sodium propionate through a fistula in the caecum during a 28-day experimental period.We characterized the effects of propionate administration on peptide YY(PYY)and glucagon-like peptide 1(GLP-1)secretion from colonic tissue,and investigated the role of propionate infusion on the expression of appetite-related genes in the colon and hypothalamus.Further,the direct impact of propionate administration on the expression of orexigenic neuropeptide agouti-related protein(AgRP)in hypothalamic N38 cells was also examined.The results showed that intra-cecal infusion of propionate reduced the short-term feed intake(P<0.05)but not the long-term feed intake in pigs(P>0.05).Propionate administration stimulated PYY and GLP-1 release from colon tissue in vivo and ex vivo(P<0.05).It also upregulated PYY expression in the colonic mucosa(P<0.05).Meanwhile,the GLP-1 and PYY levels in the blood were increased after intra-cecal infusion of propionate at d 28(P<0.05).Additionally,intra-cecal infusion of propionate upregulated the mRNA and protein expression of free fatty acid receptor 2/3(FFAR2/FFAR3)in the colonic mucosa(P<0.05).Propionate infusion also downregulated the orexigenic AgRP mRNA expression(P<0.05)and upregulated the anorexigenic cocaine-and amphetamine-regulated transcript(CART)mRNA expression(P=0.09)in the hypothalamus.Moreover,propionate administration directly downregulated AgRP expression in hypothalamic N38 cells in a dose-dependent manner(P<0.05).Collectively,these findings demonstrated that cecal propionate stimulated colonic secretion of satiety hormones and suppressed appetite to reduce the short-term feed intake in pigs.This study highlights that microbial-derived propionate exerts an important role in regulating the physical functions of the host.

Short reaction of C-peptide, glucagon-like peptide-1, ghrelin and endomorphin-1 for different style diet in type 2 diabetic patients

Background Food composition and style is changing dramatically now, which causes inappropriate secretion of hormones from brain, gastrointestinal and endo-pancreas, may be related to unbalance of glucose in blood. The aim of this study was to explore the fast response of C-peptide, glucagon-like peptide-1 （GLP-1）, ghrelin and endomorphin-1 （EM-1） to the eastern and western style meals in patients with type 2 diabetes mellitus. Methods The study enrolled 57 patients with type 2 diabetes （20 men and 37 women, mean age （67.05±8.26） years）. Eastern style meal （meal A） and western style meal （meal B） were designed to produce the fullness effect. C-peptide, GLP-1, ghrelin and EM-1 were assessed before （0 hour） and after （2 hours） each diet. Results The delta （2h-0h） of C- peptide in meal A was significantly lower than that in meal B （P=0.0004）. C-peptide, GLP-1, ghrelin and EM-1 were obviously higher before meal B than those before meal A （P 〈0.0001, 〈0.0001, =0.001, =0.0004 respectively）. Blood glucose 2 hours and 3 hours after meal B were higher than those after meal A （P=0.0005, 0.0079 respectively）. Correlations between GLP-1 and ghrelin were strongly positive before both meals and 2 hours after both meals and also in relation to the delta of meal A and meal B （rA0h=0.7838, rB05=0.9368, rA25=0.7615, rB2h=0.9409, r A（2h-0h）=0.7531, rB（2h 05）=0.9980, respectively, P 〈0.0001）. Conclusion Western style meal （high fat and protein food） could make more response of C-peptide than eastern style meal, and could stimulate more gut hormones （GLP-1, ghrelin） and brain peptide （EM-1） at the first phase of digestion.