Enterostatin deficiency increases serum cholesterol but does not influence growth and food intake in mice.

A pentapeptide released from procolipase, enterostatin, selectively attenuates dietary fat intake when administered peripherally or centrally. Enterostatin may act through the afferent vagus nerve and in the hypothalamus and amygdala, primarily in the central nucleus of the amygdala. To investigate the physiological role of endogenous enterostatin, we created an enterostatin-deficient, colipase-sufficient (Ent(-/-)) mouse. Ent(-/-) mice are viable, normally active, and fertile. They exhibit normal growth on low-fat and high-fat diets. Furthermore, Ent(-/-) mice develop diet-induced obesity, as do Ent(+/+) mice, and have normal responses to a two-macronutrient choice diet and to a switch from a high-fat to a low-fat diet. Levels of total serum (P = 0.004) and non-HDL (P

Pancreatic lipase-related protein 2 is the major colipase-dependent pancreatic lipase in suckling mice.

Suckling mice express colipase before the expression of pancreatic triglyceride lipase. Yet, efficient fat digestion in newborns requires colipase, suggesting that colipase may act as a cofactor for another lipase such as pancreatic lipase-related protein 2 (PLRP2). We determined whether PLRP2 or another lipase depends on colipase for maximal activity in newborn mice by analyzing extracts from the pancreas of 4-d-old colipase-deficient and PLRP2-deficient mice. Pancreatic extracts from colipase-deficient pups had lipase activity that was stimulated onefold by the addition of exogenous colipase (P<0.001). The activity was completely inhibited by an antibody against pancreatic triglyceride lipase that also recognizes PLRP2. In contrast, pancreatic extracts from PLRP2-deficient pups had significantly lower baseline activity and no colipase-dependent activity. The baseline activity was not inhibited by the anti-pancreatic triglyceride lipase antibody or an antibody against carboxyl ester lipase. We next separated the extracts into two fractions, one containing PLRP2 and the other devoid of PLRP2. All of the colipase-dependent activity segregated with the PLRP2-containing fraction, consistent with the conclusion that PLRP2 is the major colipase-dependent lipase in the pancreas of newborns.

Isolated lipase and colipase deficiency in two brothers.

Two brothers of Arab origin, aged 15 and 10 years, with isolated congenital lipase and colipase deficiency are described. Both were normally developed with a history of passing greasy stools since early infancy. Both have remarkable steatorrhoea and low serum carotene and vitamin E concentrations. After exocrine pancreatic stimulation, lipase and colipase activities in the duodenal fluid were almost completely absent, while amylase trypsin, bile salt, and pH values were normal. No other aetiology for exocrine pancreatic insufficiency was found. This is the first report of congenital combined lipase and colipase deficiency in two brothers.

Isolated congenital lipase-colipase deficiency.

A 5-yr-old child with isolated combined pancreatic lipase and colipase deficiency is described. The patient has a history of passing oily stools since birth. Pancreatic stimulation tests showed that both lipase and colipase activities were less than 2% of normal control values. Despite the total lack of both enzymes, the patient's fat absorption coefficient was 50%. Fat absorption coefficient increased to 82% with pancreatic enzyme supplementation. This is the first report of congenital combined lipase and colipase deficiency.

Colipase and lipase secretion in childhood-onset pancreatic insufficiency. Delineation of patients with steatorrhea secondary to relative colipase deficiency.

Pancreatic lipase and colipase secretion was assessed in 64 patients with pancreatic disease, 24 of whom had steatorrhea, and in 14 control subjects. A wide range of lipase and colipase secretion was seen in patients both with and without steatorrhea. Considerable loss of pancreatic lipase and colipase secretion had to occur before steatorrhea developed, as the highest hourly secretion of lipase and colipase in this group of patients was less than 4% and less than 2%, respectively, of the lowest values recorded in normal subjects. Colipase and lipase outputs were very strongly correlated (r = 0.96) throughout the range of pancreatic function. Lipase was always unsaturated with respect to colipase, but in only a limited number of patients with relatively low pancreatic secretion was the degree of unsaturation greater than 2 standard deviations below the mean. The importance of low saturation or low colipase secretion was evident in a group of 11 patients with a narrow range of lipase secretion in a transitional zone between secretion rates associated with steatorrhea and with normal fat excretion. In this group, 7 patients were identified in whom colipase deficiency appeared to be the sole cause of steatorrhea. The correlation of colipase secretion with the level of fecal fat excretion was highly significant (p less than 0.001) and indicated that fat digestion and subsequent fat absorption depended on colipase secretion up to at least a level of 25% fecal fat excretion. Nonpancreatic factors could well govern the extent of fat absorption above this level, as colipase secretory values in this range were uniformly low.

Isolated co-lipase deficiency in two brothers.

Two normally developed Assyrian brothers with isolated pancreatic co-lipase deficiency are described. They presented at the age of 5-6 years with loose stools. They had steatorrhoea, and analysis of exocrine pancreatic enzymes in the small intestine showed co-lipase deficiency, while amylase, chymotrypsin, trypsin and lipase were normal. Intraduodenal infusion of purified co-lipase improved fat digestion measured by the triolein breath test. Their steatorrhoea diminished on treatment with enteric-coated pancreatic enzymes.