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TitleA study of pseudocholinesterase in obesity, diabetes, and nutrition : studies using experimental models
AuthorKean, Kenneth Thomas
DescriptionThesis (M.Sc.) -- Memorial University of Newfoundland, 1985. Medicine
Paginationxii, 104 leaves
SubjectCholinesterases; Lipids--Metabolism; Obesity;
Degree GrantorMemorial University of Newfoundland. Faculty of Medicine
NotesBibliography : leaves 94-104.
AbstractHuman serum pseudocholinesterase (PChE) has been widely studied for its genetic polymorphism, but studies defining its physiological role have not been successful. The origin of plasma PChE is the liver. Human serum PChE has been reported to be increased in hyperlipoproteinemia and obesity. -- A relationship between food assimilation and PChE was proposed on the basis of dietary experiments in mice. Further studies in hyperphagic obese mice showed that both serum and liver PChE activity increased in response to overeating. However, adipose tissue PChE activity is decreased in obese mice. -- Whether such alterations are evident in genetically (Zucker) fat (fa/fa) rats is not known. What is the age of obviously altered PChE activity in the liver and adipose tissue of the postweanling genetically obese (ob/ob) mouse? What is the sub-cellular location of PChE in the liver of ob/ob mice? Whether dietary protein, carbohydrate, or fat influences PChE induction in the liver is not clear. What effect does specific inhibition of PChE have on epinephrine-stimulated lipolysis? -- Male fa/fa rats and ob/ob mice were used as experimental models of obesity and diabetes. Dietary studies were done in male Swiss-Webster mice. Isolated rat adipocytes were used to study the effect of specific inhibition of PChE on epinephrine-stimulated lipolysis in vitro. -- PChE was determined by a colorimetric method. Sub-cellular changes in liver PChE of ob/ob mice were analyzed by a cytochemical method for electron microscopy. Rate of glycerol release was used as an indicator of rate lipolysis. Glycerol was determined by a colorimetric enzymatic method. -- Serum and liver PChE activity is significantly higher (P 0.01) in fa/fa rats when compared to lean rats. Adipose tissue PChE activity was not significantly different between the two groups. Linear regression analysis showed that serum PChE activity has a good positive correlation with liver PChE activity, serum triglycerides, body weight and food intake. -- Liver PChE activity was significantly higher (P 0.05) in ob/ob mice than in lean littermates as early as 23 days of age. Adipose tissue PChE activity was, on the other hand, significantly lower (P 0.05) in ob/ob mice than in lean littermates as early as 23 days of age. By cytochemical electron microscopy, increased staining for PChE was observed in the rough endoplasmic reticulum of ob/ob mice. Albino mice with different diets showed that high protein diets produced the greatest increase in PChE activity in the liver compared to high carbohydrate or high fat diets. Mice fed a normal mouse diet ad libitum had significantly higher (P 0.05) liver PChE activity than those fed a restricted diet of 2g of normal mouse chow per day. In albino mice, liver PChE activity varied directly with the protein content in the diet. -- A significantly higher (P 0.05) release of glycerol from rat adipocytes was observed, as expected, in the presence of epinephrine when compared to basal conditions. Propranolol, a beta-adrenoreceptor blocker, decreased the release of glycerol significantly (P 0.05) and also inhibited PChE. The specific PChE inhibitor tetramoneisopropylpyrophosphoramide (Iso-OMPA) also significantly decreased (P 0.05) the epinephrine-stimulated lipolysis. Purified horse serum PChE showed no lipase activity and Iso-OMPA had no significant effect on the lipase activity of purified triacylglycerol acylhydrolase (lipase) in vitro. -- Genetically obese (fa/fa) rats show alterations in PChE activity similar to that observed in obese human beings and mice. Liver and adipose tissue PChE activity are altered in ob/ob mice before frank expression of obesity is evident. Increased synthesis is the apparent cause of increased liver PChE activity in the ob/ob mouse. Further confirmation requires studies using immune-precipitation techniques. Dietary studies suggest that liver PChE induction is a function of the level of protein in the diet. Specific inhibition of PChE causes a decrease in epinephrine-stimulated lipolysis. The effect of propranolol and Iso-OMPA suggest a relationship between PChE and the beta-adrenoreceptor in adipose tissue.
Resource TypeElectronic thesis or dissertation
FormatImage/jpeg; Application/pdf
SourcePaper copy kept in the Centre for Newfoundland Studies, Memorial University Libraries
Local Identifier75348984
RightsThe author retains copyright ownership and moral rights in this thesis. Neither the thesis nor substantial extracts from it may be printed or otherwise reproduced without the author's permission.
CollectionElectronic Theses and Dissertations
Scanning StatusCompleted
PDF File(22.15 MB) --
CONTENTdm file name317802.cpd