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PubMed1993

Use of pup in a cup model to study gastrointestinal development: interaction of nutrition and pituitary hormones.

The novel technique of artificial rearing (AR) of rat pups circumvents the difficulty of controlling diet composition and caloric intake. For studies of effects of nutrition and hormone interactions on gastrointestinal development, an appropriate experimental approach is to use AR rats whose corticosterone production is inhibited or abolished. Hypophysectomized (Hx) rats were used to examine whether growth retardation after Hx results from reduced caloric intake. Hx, sham-Hx and intact rats were isocalorically fed a cow-milk formula from day 12 to 18. Mother-fed (MF) Hx and intact rats were used as baseline controls. MF-Hx showed retarded intestinal growth, decreased body weight gain and reduced skeletal growth. In contrast, AR-Hx rats showed intestinal hypertrophy, normal body weight gain and reduced skeletal growth. Intestinal lactase activity remained higher in MF-Hx or AR-Hx rats than in control groups. AR-Hx rats showed no precocious increase of intestinal maltase and sucrase activity as did AR controls. Trace levels of serum growth hormone was detectable in MF-Hx but not in AR-Hx rats. We conclude that caloric intake can promote intestinal and somatic growth in the absence of the pituitary gland and pituitary hormones are required for skeletal growth and intestinal enzymic differentiation.

Animals↗
PubMed1995

Lipase inhibition and hormonal status, body composition and gastrointestinal processing of a liquid high-fat mixed meal in moderately obese subjects.

The effect of Orlistat, a lipase inhibitor used in the treatment of obesity was studied on gastrointestinal transit time, on body composition and on hormones known to be influenced by the degree of hydrolysis of nutritional triglycerides or by reduced nutrient intake and absorption. After a placebo run-in period 14 patients were randomized to a 12-week treatment period on Orlistat 360 mg per day (mean body weight 93.1 +/- 9.8 kg) or placebo (mean body weight 90.7 +/- 10.5 kg). At randomization and after 12 weeks body weight, body composition, thyroid hormones, catecholamines, insulin-like growth factor I (IGF-I) and IGF-binding protein 3 were measured. During 4 hours after consumption of a liquid fat-rich mixed meal containing study medication, 15 g lactulose and 25 g xylose, blood levels of glucose, insulin, c-peptide, glucagon, triglycerides, free fatty acids, cholecystokinin, pancreatic polypeptide and xylose and expiration air levels of hydrogen were measured. Weight loss was 4.2 +/- 3.5 kg in the Orlistat group versus 3.0 +/- 1.9 kg in the placebo group. Fat mass decreased to an equal degree, whereas lean body mass remained stable. No differences were found for thyroid hormones, catecholamines, IGF-I and IGFBP-3 levels. By comparing the areas under the curve (AUC) and the peak levels at randomization (acute effects) of insulin and c-peptide a tendency was found to be increased in the Orlistat group, whereas those of xylose were increased significantly, suggesting faster gastric emptying after Orlistat. No differences were found in the other parameters. By comparing the changes in responses (longer term effects) no significant differences were found. In conclusion, the presence in the gut of undigested and unabsorbed fat does not seem to have a relevant influence on hormonal status and body composition in a small group of moderately obese patients.

Body Composition↗
PubMedDate not supplied

Structure-activity studies of peptide YY(22-36): N-alpha-Ac-[Phe27]PYY(22-36), a potent antisecretory peptide in rat jejunum.

Peptide YY (PYY) and its homologous peptide, neuropeptide Y (NPY), are known to exhibit potent antisecretory effects in the intestine. To determine the structural requirements to elicit antisecretory effects, we have synthesized several analogs of the PYY active site, PYY(22-36), and compared their binding affinities and antisecretory potencies in rat jejunum. These investigations revealed that the hydroxyl groups of Ser23 and Thr32, as well as the imidazole group of His26, are important for activity in the intestine. N-alpha-acetylation of PYY(22-36) increased both the binding affinity and antisecretory potency. Structure-activity studies with N-alpha-Ac-PYY(22-36) showed that substitution of His26 with parachlorophenylalanine (pCl-Phe) or Tyr36 with N-Me-Tyr reduced receptor affinity, while replacement of Tyr27 with Phe increased the activity substantially. Furthermore, acylation of the alpha-NH2 group with hydrophobic groups, myristic and naphthaleneacetic acids, substantially reduced the antisecretory potencies but not the binding affinities. Further modification of N-alpha-Ac-[Phe27]PYY(22-36) may lead to the development of more potent agonist compounds, which may provide a framework for the design of a new class of antidiarrheal drugs.

Animals↗