Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0024523 (malabsorption)
 7,319 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Plasma lipoproteins and postheparin plasma were investigated in a patient with familial LCAT deficiency with normal renal function and without proteinuria. As revealed by gelfiltration the large molecular weight LDL2 was not present, and myelin structures were not found in LDL1 or LDL2 when she was on her ordinary diet. After 60--65% fat diet for one week the large molecular LDL2 was found, but only in low concentration. We have no explanation for the difference in the lipoprotein abnormalities of this patient and others with this disease. There is no major difference in the fat content in the ordinary diet of the Norwegian patients with familial LCAT deficiency, nor has our patient any clinical signs of malabsorption. Furthermore, there was no difference in lipoprotein lipase or hepatic lipase activity in postheparin plasma between our patient and others with the same disease. However, whereas hepatic lipase activity was within the reference values, lipoprotein lipase activity was rather low in all patients investigated. We suggest that impaired VLDL catabolism in plasma, because of LCAT deficiency and low lipoprotein lipase activity, may partly explain the low HDL concentration consistently found in patients with familial LCAT deficiency.
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PMID:Familial lecithin:cholesterol acyltransferase deficiency. Further studies on plasma lipoproteins and plasma postheparin lipase activity of a patient with normal renal function. 21 75

A new kindred with asymptomatic hypobetalipoproteinemia is reported. The proband, age 67, differs from previously described cases in several respects: (a) unusually low levels of low density lipoprotein (LDL) cholesterol (4-8 mg/dl); (b) normal triglyceride levels; (c) low levels of high density lipoprotein; (d) mild fat malabsorption; and (e) a defect in chylomicron clearance. On a high-carbohydrate diet his plasma triglyceride levels, instead of rising, actually fell. Turnover of triglycerides in very low density lipoproteins (VLDL) was low (2.8 mg/kg per h). Fractional catabolic rate of LDL protein was just above the normal range (0.655/d) but net turnover was <10% of normal (0.65 mg/kg per d). The half-life of his chylomicrons was 29 min, five times the normal value. Postheparin lipoprotein lipase activity was normal and apolipoprotein C-II, the activator protein for lipoprotein lipase, was present and functional. Apolipoprotein C-III(1), however, was not detected in the VLDL fraction, a finding previously reported in patients with abetalipoproteinemia. Fecal excretion of cholesterol was almost twice normal; total sterol balance was increased by congruent with40%. The unusual features in the proband that distinguish him from previously described cases and from his affected first-degree relatives suggested that, in addition to the basic gene defect affecting LDL metabolism, he might have a second abnormality affecting clearance of chylomicrons and VLDL. The ratio of apolipoprotein E(3) to E(2) in his VLDL fraction was 0.93, just below the lower limit of normal, suggesting heterozygosity for E(3) deficiency. Whether or not this contributes to his hypertriglyceridemia remains to be established.
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PMID:Metabolic studies in an unusual case of asymptomatic familial hypobetalipoproteinemia with hypolphalipoproteinemia and fasting chylomicronemia. 22 46

The use of medium-chain triglycerides (MCT) in lipid malabsorption and lipoproteinlipase deficiency is well established. It is known from experiments in animals and humans that after parenteral administration MCT are rapidly hydrolyzed by lipoprotein lipase in plasma. The liberated medium-chain fatty acids are taken up independently of carnitine by mitochondria and oxidized to CO2 in extrahepatic tissues more rapidly than long-chain fatty acids. Medium-chain fatty acids are ketogenic, and consequently both medium-chain fatty acids and ketones are carnitine-independent energy carriers for different tissues. By simultaneously infusing glucose the risk of ketoacidosis can be minimizes. MCT in parenteral nutrition is a substrate which provides high-density energy without problems regarding osmolality or renal losses and with less interference to the reticulohistiocytes of the immune system. On the basis of these metabolic and functional properties MCT represent a valuable additional energy source in total parenteral nutrition.
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PMID:[Medium-chain triglycerides--useful energy carriers in parenteral nutrition]. 249 24

Within 1 hr of intraperitoneal administration of 1 microgram 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD)/kg, lipoprotein lipase (LPL) activity was reduced 38% from initial levels in the adipose tissue of the guinea pig. Maximal depression was observed after 2 days and persisted throughout the 10-day observation period. Oral administration of glucose restored LPL activity in TCDD-treated animals after 1 day but only partially after 2 and 5 days, and had no effect after 10 days of exposure. Although initial (2-day) serum insulin levels were depressed, the inability of glucose to restore LPL activity after prolonged exposure was not due to malabsorption of glucose nor to changes in serum thyroxine or insulin concentration. TCDD also inhibited the lipolytic pathway in the adipocyte, but had no effect on hormone sensitive lipase (HSL). Since HSL and LPL are reciprocally regulated, it was concluded that TCDD acts on the adipocyte to uncouple HSL-LPL reciprocity as well as to reduce LPL production.
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PMID:Reduction of adipose tissue lipoprotein lipase activity as a result of in vivo administration of 2,3,7,8-tetrachlorodibenzo-p-dioxin to the guinea pig. 328 12

In the past we have shown that patients with chronic renal failure (CRF) on hemodialysis show evidence of intestinal malabsorption of fat. The present study was designed to verify this finding in an animal model. Male rats weighing +/- 200 g were studied. Uremia (U) was induced by 2-stage subtotal (5/6) nephrectomy. Control (C) animals were sham-operated. Fat absorption was studied after 6 weeks of uremia with the oral fat loading test. Twenty percent intralipid (0.25 g/100 gBW) was given by gastric tube feeding to fasting animals and the appearance of chylomicrons (CHYL) and the rise of triglycerides (TG) in the serum was followed for 5 hrs. In order to isolate the effect of fat absorption, an additional group of U and C animals was pretreated with orotic acid and triton, thus blocking hepatic TG synthesis and neutralizing peripheral lipoprotein lipase activity. The absorption of CHYL was significantly (p less than 0.01) impaired in all U animals and averaged 43 and 70 percent of that of the C animals, 1 and 2 hrs after the load respectively. The rise in serum TG did not differ from C in mildly U animals (Scr 1.0 +/- 0.04). In the more severely uremic animals (Scr 2.6 +/- 0.2), however, pretreated with orotic acid and triton, the rise in serum TG was far less (p less than 0.01) than in C animals (111 +/- 26-903 +/- 111 delta % V.780 +/- 170-5032 +/- 746 delta %) 1 and 5 hrs after the load.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Intestinal fat malabsorption in the uremic rat. 342 36

Carbohydrate and lipid metabolism were studied in 10 patients who had undergone total pancreatectomy. The results were compared with Type I diabetic patients and normal subjects, all of whom were matched for age, sex and weight. At the same level of glycemic control, the daily need for insulin was significantly lower in the patients with pancreatogenic diabetes than in those with Type I diabetes. Concentrations of serum total VLDL and HDL triglyceride were higher in the pancreatectomized patients than in the diabetic or normal controls, whereas concentrations of serum total and LDL cholesterol were significantly lower. The composition of the VLDL, LDL and HDL particles was abnormal in the totally pancreatectomized patients as all three lipoprotein fractions were enriched in triglyceride. HDL2 cholesterol was similar in the totally pancreatectomized patients to that in the other two groups but HDL3 cholesterol was lower. Postheparin plasma lipoprotein lipase and hepatic lipase activities were normal. It is concluded that in totally pancreatectomized patients the changes in the lipoprotein profile on reflect more the action of various confounding factors, i.e. malabsorption, continuance of alcohol abuse and dietary changes than the impact of the diabetes itself.
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PMID:Glycemic control and serum lipoproteins after total pancreatectomy. 405 43

Raised plasma triglycerides (TGs) and nonesterified fatty acid (NEFA) concentrations are thought to play a role in the pathogenesis of insulin-resistant diabetes. We report on two sisters with extreme hypertriglyceridemia and overt diabetes, in whom surgical normalization of TGs cured the diabetes. In all of the family members (parents, two affected sisters, ages 18 and 15 years, and an 11-year-old unaffected sister), we measured oral glucose tolerance, insulin sensitivity (by the euglycemic-hyperinsulinemic clamp technique), substrate oxidation (indirect calorimetry), endogenous glucose production (by the [6,6-2H2]glucose technique), and postheparin plasma lipoprotein lipase (LPL) activity. In addition, GC-clamped polymerase chain reaction-amplified DNA from the promoter region and the 10 coding LPL gene exons were screened for nucleotide substitution. Two silent mutations were found in the father's exon 4 (Glu118 Glu) and in the mother's exon 8 (Thr361 Thr), while a nonsense mutation (Ser447 Ter) was detected in the mother's exon 9. Mutations in exons 4 and 8 were inherited by the two affected girls. At 1-2 years after the appearance of hyperchylomicronemia, both sisters developed hyperglycemia with severe insulin resistance. Because medical therapy (including high-dose insulin) failed to reduce plasma TGs or control glycemia, lipid malabsorption was surgically induced by a modified biliopancreatic diversion. Within 3 weeks of surgery, plasma TGs and NEFA and cholesterol levels were drastically lowered. Concurrently, fasting plasma glucose levels fell from 17 to 5 mmol/l (with no therapy), while insulin-stimulated glucose uptake, oxidation, and storage were all markedly improved. Throughout the observation period, plasma TG levels were closely correlated with both plasma glucose and insulin concentrations, as measured during the oral glucose tolerance test. These cases provide evidence that insulin-resistant diabetes can be caused by extremely high levels of TGs.
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PMID:Triglyceride-induced diabetes associated with familial lipoprotein lipase deficiency. 1034 13

Upon high-fat feeding, prostaglandin E receptor subtype 4 (EP4)-knockout mice gain less body weight than their EP4(+/+) littermates. We investigated the cause of the lean phenotype. The mice showed a 68.8% reduction in weight gain with diminished fat mass that was not attributable to reduced food intake, fat malabsorption, or increased energy expenditure. Plasma triglycerides in the mice were elevated by 244.9%. The increase in plasma triglycerides was independent of changes in hepatic very low density lipoprotein (VLDL)-triglyceride production or intestinal chylomicron-triglyceride synthesis. However, VLDL-triglyceride clearance was drastically impaired in the EP4-knockout mice. The absence of EP4 in mice compromised the activation of lipoprotein lipase (LPL), the key enzyme responsible for trafficking of plasma triglycerides into peripheral tissues. Deficiency in EP4 reduced hepatic mRNA expression of the transcriptional factor cAMP response element binding protein H (by 36.8%) and LPL activators, including apolipoprotein (Apo)a5 (by 40.2%) and Apoc2 (by 61.3%). In summary, the lean phenotype of EP4-deficient mice resulted from reduction in adipose tissue and accretion of other peripheral organs caused by impaired triglyceride clearance. The findings identify a new metabolic dimension in the physiologic role played by endogenous EP4.
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PMID:Mice lacking prostaglandin E receptor subtype 4 manifest disrupted lipid metabolism attributable to impaired triglyceride clearance. 2627 Dec 53