leptin and Short-Bowel-Syndrome

Obesity may protect against the nutritional consequences of short bowel syndrome. We hypothesized that rats preconditioned with an obesogenic diet would have better outcomes after surgical induction of short bowel syndrome compared to rats on regular chow. Rats were fed a high-fat diet or regular rat chow for six months, and then underwent 50% proximal, 50% distal, or sham enterectomy. Food intake, weight, and body composition were monitored before and for 4 weeks after surgery. The high-fat diet consistently produced obesity (>25% body fat). All procedures induced weight loss, but there was no discernable difference between resection vs. sham resection. Rats on the high-fat diet had a greater post-resection loss of body fat compared to rats on chow (36 vs. 26 g, respectively). There was a nonsignificant trend of less lean mass loss in the former compared to the latter rats (16 vs. 33 g, respectively). Enterectomy moderated serum ghrelin, GIP, PPY, insulin, and leptin. Intestinal adaptation was not different between obese vs. non-obese rats. Rats preconditioned with the high-fat diet may have had better retention of lean body mass after a surgical procedure compared to rats on chow. The effect of 50% enterectomy was less than expected.

Topics: Animals; Body Fat Distribution; Diet, High-Fat; Eating; Energy Intake; Gastric Inhibitory Polypeptide; Ghrelin; Insulin; Intestine, Small; Leptin; Male; Obesity; Pancreatic Polypeptide; Rats; Rats, Sprague-Dawley; Short Bowel Syndrome

Recent evidence suggests that the adipose tissue-derived cytokine leptin (LEP) is involved in modulation of growth and differentiation of normal small intestine. The purpose of the present study was to evaluate the effects of parenteral LEP on structural intestinal adaptation, cell proliferation and apoptosis in a rat model of short bowel syndrome (SBS). Male Sprague-Dawley rats were divided into three experimental groups: Sham rats underwent bowel transection and re-anastomosis, SBS-rats underwent a 75% small bowel resection, and SBS-LEP-rats underwent bowel resection and were treated with LEP given subcutaneously at a dose of 20 mug/kg, once daily, from day 3 through 14. Parameters of intestinal adaptation (bowel and mucosal weights, mucosal DNA and protein, villus height and crypt depth in jejunum and ileum), enterocyte proliferation and enterocyte apoptosis were determined on day 15 following operation. Ileal tissue samples were taken for detection of bax and bcl-2 gene expression using RT-PCR technique. Statistical analysis was performed using the non-parametric Kruskal-Wallis ANOVA test, with P<0.05 considered statistically significant. Treatment with subcutaneous LEP resulted in a significant increase in jejunal (17%, P<0.05) and ileal (13%, P<0.05) bowel weight, jejunal (10%, P<0.05) and ileal (25%, P<0.05) mucosal weight, jejunal (26%, P<0.05) and ileal (38%, P<0.05) mucosal DNA, ileal (25%, P<0.05) mucosal protein, jejunal (41%, P<0.05) and ileal (21%, P<0.05) villus height, jejunal (37%, P<0.05) crypt depth, and jejunal (24%, P<0.05) and ileal (21%, P<0.05) enterocyte proliferation compared to SBS-animals. Enterocyte apoptosis increased significantly after bowel resection in jejunum and ileum compared to sham animals and was accompanied by an increased bax gene expression and a decreased bcl-2 gene expression in ileal samples. SBS-LEP rats showed a trend toward a decrease in enterocyte apoptosis in ileum and a mild decrease in bax gene expression compared to SBS-untreated animals. In conclusion, in a rat model of SBS parenteral LEP stimulates structural intestinal adaptation. Increased cell proliferation and decreased cell death via apoptosis may be responsible for this increased cell mass.

Topics: Adaptation, Physiological; Analysis of Variance; Animals; Apoptosis; Cell Proliferation; Enterocytes; Hyperplasia; Intestinal Mucosa; Leptin; Male; Random Allocation; Rats; Rats, Sprague-Dawley; Short Bowel Syndrome; Statistics, Nonparametric

Ghrelin is a peptide hormone that is involved in regulating growth hormone secretion as well as food intake and energy homeostasis. The aim of this study was to compare changes in plasma ghrelin levels in patients with malnutrition due to anorexia nervosa (AN) or short bowel syndrome (SBS). Blood samples for laboratory analyses were taken from 16 AN patients (plus 13 comparable healthy controls) and 27 SBS patients (plus 13 comparable healthy controls) after an overnight fast. In comparison with their respective control groups, plasma ghrelin levels were increased in the AN patients (p < 0.05) and significantly decreased in the patients with SBS (p < 0.01). These results suggest that quantitative ghrelin secretion in the gut wall is important in determining ghrelin concentrations in the systemic circulation.

Topics: Adipose Tissue; Adult; Anorexia Nervosa; Body Composition; Body Mass Index; Case-Control Studies; Fasting; Female; Ghrelin; Growth Hormone; Humans; Insulin-Like Growth Factor Binding Protein 1; Insulin-Like Growth Factor Binding Protein 3; Insulin-Like Growth Factor I; Leptin; Male; Malnutrition; Middle Aged; Nutrition Assessment; Peptide Hormones; Receptors, Cell Surface; Receptors, Leptin; Sex Characteristics; Short Bowel Syndrome; Skinfold Thickness

Leptin is a 16-kDa peptide produced by adipocytes that plays an important role in the regulation of body fat and satiety. We have previously shown that leptin is a growth factor for normal rat small intestine. This study was designed to examine the effect of systemic leptin administration on small bowel absorptive function after massive small bowel resection (MSBR).. Twenty-one adult male Sprague-Dawley rats underwent an 80% small bowel resection and end-to-end jejunoileal anastomosis. Seven days following resection, all rats had placement of a jugular venous catheter connected to a subcutaneously placed osmotic minipump and were divided into three groups based on the content of each minipump: Group 1 (n = 7) 0.1% bovine serum albumin; Group 2 (n = 7) leptin 2 microg/kg/day; and Group 3 (n = 7) leptin 4 microg/kg/day. Following a 14-day infusion period, [(14)C]galactose absorption was measured using a closed-recirculation technique. Mucosal DNA content was determined for all groups using a standard DNA purification kit. Mucosal RNA was extracted and RT-PCR was performed using the following primers: sodium/glucose cotransporter (SGLT-1), fructose transporter (GLUT-5), and glyceraldehyde-3-phosphate dehydrogenase, an internal standard. PCR products were separated on a 4% agarose gel and relative band intensities were measured. Statistical analysis was performed using ANOVA and expressed as means +/- SEM.. Group 2 showed a 44% increase in galactose absorption (P < 0.01) and a 14% increase in GLUT-5 band intensity (P < 0.05), but no change in DNA content or SGLT band intensity.. This study demonstrates for the first time that leptin enhances small intestine carbohydrate absorption beyond the normal adaptive response following MSBR. Leptin may be clinically useful in patients with inadequate intestinal function.

Topics: Adaptation, Physiological; Adipocytes; Animal Nutritional Physiological Phenomena; Animals; Carbon Radioisotopes; Galactose; Gene Expression; Glucose Transporter Type 5; Growth Substances; Intestinal Absorption; Intestine, Small; Leptin; Male; Monosaccharide Transport Proteins; Rats; Rats, Sprague-Dawley; Short Bowel Syndrome

Short-bowel syndrome is a state of severe malabsorption resulting from absence or removal of the small bowel for several causes. A number of short-bowel patients develop hyperphagia. Leptin, a protein secreted from adipose tissue, signals the amount of energy stores to the brain.. To study body composition and leptin regulation in short-bowel patients and to determine whether or not leptin concentrations are linked with hyperphagia.. We studied 25 short-bowel patients (remnant bowel less than 150 cm) and 31 controls and 10 oral nutrition. Fifteen patients received total parenteral nutrition and 10 oral nutrition. Anthropometric measurements, body composition (by bioelectrical impedance), and cholesterol, triacylglycerol and leptin concentrations were studied in all subjects.. There were no differences between short-bowel patients and controls in anthropometric variables, body composition, or leptin concentrations. Leptin concentrations were higher in short-bowel women than men (9.21+/-8.54 vs. 3.22+/-1.86 ng/ml, P=0.01). Leptin concentrations correlated positively with age (r=0.4, P=0.045), body mass index (r=0.52, P=0.007), fat mass (r=0.67, P=0.001) and body fat (r=0.68, P=0.0001); there were no correlations with other body composition parameters. We found no correlations between parenteral or oral nutrition and body composition parameters, or between leptin concentrations and the presence of hyperphagia. Logistic regression analysis showed that body fat correctly identified leptin concentrations in 60% of patients.. Body composition, leptin concentrations and leptin regulation in patients with short-bowel syndrome are similar to those of controls. Leptin concentrations do not correlate with hyperphagia in short bowel-patients.

Topics: Adipose Tissue; Adult; Age Factors; Aged; Anthropometry; Body Composition; Body Mass Index; Cholesterol; Electric Impedance; Female; Humans; Hyperphagia; Leptin; Male; Middle Aged; Nutritional Support; Regression Analysis; Sex Factors; Short Bowel Syndrome; Triglycerides