leptin and Intestinal-Diseases

To investigate the mechanism of Ghrelin/GHS-R signaling pathway in small intestine injury induced by NSAIDs related enteropathy. To clarify the mechanism network of intestinal mucosal repair with naringin as a new therapeutic method.. Naringin was used as the intervention method, observed the damage of small intestinal mucosa and detected the expression of ghrelin, GHS-R, leptin and TNF-α by electron microscopy, HE staining and immunohistochemistry.. Compared with the control group, the weight of rats in the model group decreased, the thickness of intestinal mucosa became thinner, the structure of intestinal mucosa changed, the expression of ghrelin, GHS-R and leptin decreased, the expression of TNF-α increased. Compared with the model group, the intestinal mucosa of the treatment group was repaired, the expression of ghrelin, GHS-R and leptin was increased, and the expression TNF-α was decreased.. The mechanism of intestinal mucosal damage in patients with NSAIDs related enteropathy may be related to the decreased expression of ghrelin, GHS-R and leptin, and promotion of TNF-α secretion. Naringin can effectively promote the secretion of ghrelin and leptin, the expression of GSH-R, and inhibit the release of TNF-α, so as to repair intestinal mucosa naringin will become a new method to treat and prevent NSAIDs related intestinal diseases.

Topics: Animals; Anti-Inflammatory Agents, Non-Steroidal; Flavanones; Ghrelin; Intestinal Diseases; Intestine, Small; Leptin; Male; Protective Agents; Rats; Rats, Sprague-Dawley; Receptors, Ghrelin; Tumor Necrosis Factor-alpha

Environmental enteric dysfunction (EED) limits the Sustainable Development Goals of improved childhood growth and survival. We applied mucosal genomics to advance our understanding of EED.. The Study of Environmental Enteropathy and Malnutrition (SEEM) followed 416 children from birth to 24 months in a rural district in Pakistan. Biomarkers were measured at 9 months and tested for association with growth at 24 months. The duodenal methylome and transcriptome were determined in 52 undernourished SEEM participants and 42 North American controls and patients with celiac disease.. After accounting for growth at study entry, circulating insulin-like growth factor-1 (IGF-1) and ferritin predicted linear growth, whereas leptin correlated with future weight gain. The EED transcriptome exhibited suppression of antioxidant, detoxification, and lipid metabolism genes, and induction of anti-microbial response, interferon, and lymphocyte activation genes. Relative to celiac disease, suppression of antioxidant and detoxification genes and induction of antimicrobial response genes were EED-specific. At the epigenetic level, EED showed hyper-methylation of epithelial metabolism and barrier function genes, and hypo-methylation of immune response and cell proliferation genes. Duodenal coexpression modules showed association between lymphocyte proliferation and epithelial metabolic genes and histologic severity, fecal energy loss, and wasting (weight-for-length/height Z < -2.0). Leptin was associated with expression of epithelial carbohydrate metabolism and stem cell renewal genes. Immune response genes were attenuated by giardia colonization.. Children with reduced circulating IGF-1 are more likely to experience stunting. Leptin and a gene signature for lymphocyte activation and dysregulated lipid metabolism are implicated in wasting, suggesting new approaches for EED refractory to nutritional intervention. ClinicalTrials.gov, Number: NCT03588013. (https://clinicaltrials.gov/ct2/show/NCT03588013).

Topics: Biomarkers; Case-Control Studies; Celiac Disease; Cell Proliferation; Child Development; Child, Preschool; Creatinine; DNA Methylation; Epigenome; Female; Ferritins; Genomics; Growth Disorders; Humans; Infant; Infant, Newborn; Insulin-Like Growth Factor I; Intestinal Diseases; Intestinal Mucosa; Leptin; Lipid Metabolism; Lymphocyte Activation; Lymphocytes; Male; Malnutrition; Oxidative Stress; Pakistan; Transcriptome

The mechanisms of alcohol-mediated advanced liver injury in HIV-infected individuals are poorly understood. Thus, this study was aimed to investigate the effect of binge alcohol on the inflammatory liver disease in HIV transgenic rats as a model for simulating human conditions. Female wild-type (WT) or HIV transgenic rats were treated with three consecutive doses of binge ethanol (EtOH) (3.5 g/kg/dose oral gavages at 12-h intervals) or dextrose (Control). Blood and liver tissues were collected at 1 or 6-h following the last dose of ethanol or dextrose for the measurements of serum endotoxin and liver pathology, respectively. Compared to the WT, the HIV rats showed increased sensitivity to alcohol-mediated gut leakiness, hepatic steatosis and inflammation, as evidenced with the significantly elevated levels of serum endotoxin, hepatic triglycerides, histological fat accumulation and F4/80 staining. Real-time PCR analysis revealed that hepatic levels of toll-like receptor-4 (TLR4), leptin and the downstream target monocyte chemoattractant protein-1 (MCP-1) were significantly up-regulated in the HIV-EtOH rats, compared to all other groups. Subsequent experiments with primary cultured cells showed that both hepatocytes and hepatic Kupffer cells were the sources of the elevated MCP-1 in HIV-EtOH rats. Further, TLR4 and MCP-1 were found to be upregulated by leptin. Collectively, these results show that HIV rats, similar to HIV-infected people being treated with the highly active anti-retroviral therapy (HAART), are more susceptible to binge alcohol-induced gut leakiness and inflammatory liver disease than the corresponding WT, possibly due to additive or synergistic interaction between binge alcohol exposure and HIV infection. Based on these results, HIV transgenic rats can be used as a surrogate model to study the molecular mechanisms of many disease states caused by heavy alcohol intake in HIV-infected people on HAART.

Topics: Animals; Cells, Cultured; Central Nervous System Depressants; Chemokine CCL2; Dose-Response Relationship, Drug; Ethanol; Female; Gene Expression; Hepatocytes; HIV; HIV Infections; Humans; Intestinal Diseases; Intestinal Mucosa; Intestines; Leptin; Liver Diseases, Alcoholic; Permeability; Rats, Inbred F344; Rats, Transgenic; Reverse Transcriptase Polymerase Chain Reaction; Toll-Like Receptor 4

Recent evidence suggests that the adipose tissue derived cytokine leptin (LEP) is involved in the modulation of growth and differentiation of normal small intestine. The purpose of the present study was to examine the effect of leptin on enterocyte turnover and intestinal recovery after ischemia-reperfusion (IR) injury in a rat. Male Sprague-Dawley rats were divided into three experimental groups: (1) sham rats underwent laparotomy, (2) IR-rats underwent occlusion of both superior mesenteric artery and portal vein for 30 min followed by 24 h of reperfusion, and (3) IR-LEP rats underwent IR and were treated with leptin given subcutaneously at a dose of 50 microg/kg once a day for 48 h before and 24 h following IR. Intestinal structural changes, enterocyte proliferation and enterocyte apoptosis were determined 24 h following IR. A non-parametric Kruskal-Wallis ANOVA test was used for statistical analysis with P < 0.05 considered statistically significant. Treatment with leptin resulted in a significant increase in bowel weight in ileum, mucosal weight in jejunum and ileum, mucosal DNA content in ileum, mucosal protein content in jejunum and ileum, villus height in jejunum and ileum, and crypt depth in jejunum compared to IR-animals. IR-LEP rats also had a significantly lower intestinal injury score as well as lower apoptotic index and higher cell proliferation index in jejunum and ileum compared to the IR-animals. In conclusion, pre-treatment with leptin prevents gut mucosal damage and improves intestinal rehabilitation following intestinal IR in a rat.

Topics: Analysis of Variance; Animals; Apoptosis; Cell Proliferation; Disease Models, Animal; Enterocytes; Intestinal Diseases; Intestinal Mucosa; Intestine, Small; Leptin; Male; Random Allocation; Rats; Rats, Sprague-Dawley; Recovery of Function; Reperfusion Injury

To assess dynamics of serum leptin concentrations (as a possible marker of stress) at some surgical patients during short perioperative period.. The serum leptin concentrations were estimated in group of patients with trauma or large bowel diseases in stress of both own disease and next elective or urgent surgery. The subgroups of patients were: a) monotrauma (13), b) polytrauma (10), c) malignant (20) or d) inflammatory disease (13) of large bowel. The serum leptin concentrations were evaluated preoperatively and during 16 hours postoperatively-immediately after surgery, after 8 and 16 hours after operation. The serum IL-6 concentrations were estimated immediately and 48 hours postoperatively.. The serum leptin concentrations showed a time depending dynamic phase: they decreased postoperatively and increased during the first 16 hours postoperatively. It was more expressed in the malignant bowel disease subgroup. A correlation between age and serum leptin concentrations was not found in any subgroup. We found correlation between serum leptin concentrations preoperatively and postoperatively.. The serum leptin concentrations demonstrated some dynamics in short perioperative periods. It was very considerably in patients with large bowel malignancy. Any significant difference in serum IL-6 concentrations was not discovered preoperatively and postoperatively in all subgroups.

Topics: Humans; Interleukin-6; Intestinal Diseases; Leptin; Stress, Physiological; Surgical Procedures, Operative; Wounds and Injuries