RESUMO
Cachexia is a complex medical condition characterized by significant weight loss associated with decreased body fat and protein; the condition may present itself with or without anorexia. We have isolated and partially characterized a proteoglycan (azaftig) from the urine of cancer and AIDS patients experiencing weight loss. When given to mice, the purified azaftig resulted in a significant decrease in body weight and body fat without any effect on appetite. The results of these studies show that azaftig may be one of the many factors participating in the emergence of the cachectic state.
Assuntos
Peso Corporal/efeitos dos fármacos , Caquexia/urina , Neoplasias/fisiopatologia , Proteoglicanas/urina , Redução de Peso , Síndrome da Imunodeficiência Adquirida/fisiopatologia , Síndrome da Imunodeficiência Adquirida/urina , Tecido Adiposo/efeitos dos fármacos , Animais , Humanos , Camundongos , Camundongos Endogâmicos , Neoplasias/urina , Tamanho do Órgão/efeitos dos fármacos , Proteoglicanas/isolamento & purificação , Proteoglicanas/farmacologiaRESUMO
Enterostatins, pentapeptides represented at the amino-terminus of the procolipase molecule, are derived following tryptic cleavage of the procolipase molecule in the lumen of the gut. Val-Pro-Asp-Pro-Arg or VPDPR is one such enterostatin. Despite pharmacologic studies suggesting a role for VPDPR in appetite regulation and insulin secretion, the function of this endogenous peptide has been impossible to discern due to the lack of a suitable assay. Using polyclonal antibodies raised against VPDPR and different chromatographic methods, we examined the nature and distribution of enterostatin-like immunoreactivity in rat plasma. The results reported here show for the first time the presence of VPDPR-like immunoreactivity in rat plasma. Further characterization of the plasma VPDPR-like immunoreactivity revealed that a) it is not due to APGPR, VPGPR, or VPDPR but to another peptide similar to VPDPR, and b) plasma VPDPR-like immunoreactivity may circulate bound to large carrier proteins.
Assuntos
Colipases/imunologia , Oligopeptídeos/imunologia , Precursores de Proteínas/imunologia , Animais , Colipases/sangue , Precursores Enzimáticos , Ensaio de Imunoadsorção Enzimática , Masculino , Oligopeptídeos/sangue , Precursores de Proteínas/sangue , Ratos , Ratos Sprague-DawleyRESUMO
Enterostatins [Val-Pro-Asp-Pro-Arg (VPDPR), Val-Pro-Gly-Pro-Arg (VPGPR), and Ala-Pro-Gly-Pro-Arg (APGPR)] are pentapeptides derived from the NH2-terminus of procolipase after tryptic cleavage and belong to the family of gut-brain peptides. Although enterostatin-like immunoreactivities exist in blood, brain, and gut, and exogenous enterostatins decrease fat appetite and insulin secretion in rats, the roles of these peptides in human obesity remain to be examined. To determine whether VPDPR and APGPR secretion is altered in obesity, serum VPDPR and APGPR levels were measured in 38 overnight-fasted subjects (body mass index, 17.9-54.7 kg/m2) before and after a meal. The mean fasting VPDPR in the serum of lean subjects was significantly lower than that in obese subjects [lean = 603 +/- 86 nmol/L (n = 17); obese, 1516 +/- 227 nmol/L (n = 21); P = 0.0023]. In addition, the rise in serum APGPR after a meal (postmeal/fasting ratio) was significantly higher in lean than in obese subjects [lean, 1.71 +/- 0.24 (n = 17); obese, 1.05 +/- 0.14 (n = 21); P = 0.0332]. The results of these studies show hyperenterostatinemia in obesity and a diminution in enterostatin secretion after satiety.
Assuntos
Colipases/sangue , Obesidade/sangue , Pré-Menopausa/sangue , Precursores de Proteínas/sangue , Adulto , Ingestão de Alimentos/fisiologia , Precursores Enzimáticos , Jejum , Feminino , Humanos , Oligopeptídeos/sangueRESUMO
Enterostatins, pentapeptides (Val-Pro-Asp-Pro-Arg [VPDPR], Val-Pro-Gly-Pro-Arg, Ala-Pro-Gly-Pro- Arg [APGPR], and others) derived from the amino terminus of procolipase, are endogenous to a variety of tissues and body fluids including brain, gut, blood, cerebrospinal fluid, and urine. The administration of exogenous peptides has been shown to elicit a variety of biologic activities, including a decrease in dietary fat preference and pancreatic insulin secretion. Since milk is a rich source of a variety of bioactive substances, especially peptides, we investigated the presence of enterostatin-like immunoreactivity in bovine milk. We measured enterostatins-APGPR and VPDPR-in milk from a herd of 19 cows randomly selected from the Louisiana State University Department of Dairy Science Research Herd in Baton Rouge; the results of this study show a mean peptide concentration in raw milk of 33.7 ± 2.9 ng/ml for APGPR and of 104.5 ± 16.3 ng/ml for VPDPR. A further chromatographic characterization of the nature of APGPR- and VPDPR-like immunoreactivities suggested the endogenous peptides share a common epitope with APGPR or VPDPR but are not APGPR or VPDPR. Unlike APGPR or VPDPR, the endogenous peptides were heat-labile and therefore their values were much lower in pasteurized milk.
RESUMO
Many studies clearly demonstrate inhibition of dietary fat preference by exogenous enterostatins in rodents. However, what role endogenous enterostatin, if any, may play in the regulation of fat intake is not clear. To this end, we examined whether there is a relationship between plasma enterostatin (VPDPR)-like immunoreactivity and fat preference. Additionally, since enterostatin is a product of tryptic cleavage of procolipase, we examined the effect of camostat, a protease inhibitor known to inhibit trypsin and other proteases, on dietary fat preference and plasma enterostatin concentration. The results of these studies show that while there was a significant inverse relationship between plasma enterostatin and fat preference, the effect of camostat on fat preference or plasma enterostatin concentration was not clear.