Aspects of lipid and protein metabolism in the genetically obese Zucker rat

Shargill, Narinder Singh (1982) Aspects of lipid and protein metabolism in the genetically obese Zucker rat. University of Southampton, Doctoral Thesis.

Abstract

Pre-obese fa/fa rats were identified by their decreased rectal temperatures from day 16 onwards. Fatty acid synthesis was measured in vivo by H-incorporation, and in vitro by measurements of the enzymes, glucose-6-phosphate dehydrogense-andfatty acid synthetase. Serum insulin, hepatic and adipose tissue lipogenesis in suckling pre-obese pups were low and similar to lean pups. In rats which had access to the high carbohydrate maternal diet during suckling, adipose tissue lipogenesis was increased to higher levels in pre-obese than lean pups while hepatic lipogenesis was unaltered. Serum insulins rose to similar level in both genotypes. The increased accumulation of 3H-fatty acids in the adipose tissue was shown to be entirely due to de novo synthesis. The excessive accumulation of 3H-fatty acids persisted even when uptake of circulating triglycerides was abolished by the detergent Triton WR 1339. The difference in adipose tissue lipogenesis in pre-weaned lean and pre-obese pups which had access to solid food was not abolished by lowering serum insulins by streptozotocin treatment. Insulin secretory capacity in response to a glucose load was enhanced in pre-obese rats before weaning. A study of the glucocorticoid sensitive hepatic enzymes tyrosine aminotransferase (TAT) and tryptophan dioxygenase (TO) revealed an abnormality in the levels and in the regulation of TAT in the fa/fa rats. Changes in TAT and TO activities were age dependent, and TAT activity was higher in fa/fa rats despite normal serum corticosterone concentrations. The ingestion of solid food was necessary for the elevation of TAT in fa/fa rats. Although the diurnal rhythm of TAT was similar in lean and obese rats, the responses to pair-feeding, to starvation and to tryptophan administration were different in both intact and adrenalectomised obese rats. The response of TO was normal in all the dietary and hormonal influences studied. Both the time course and the dose response curve for the induction of TAT in adrenalectomised rats by corticosterone were different in obese rats. Maximum induction after a single dose (S mg/lOO g body wt.) occurred after 6 hours in lean and after 9 hours in obese rats. The induced levels of TAT in obese rats were 5-6 fold higher than lean values, and were due to increases in the amount of enzyme protein. The half life of TAT was similar in lean and obese rats suggesting that the elevated levels of TAT were due to an increase in enzyme synthesis. The exaggerated responses of TAT to corticosterone in obese rats occurred despite normal glucocorticoid receptor binding. The results are discussed in relation to the altered lipid and protein deposition in the Zucker obese rats, and the role played by adrenal glucocorticoids.

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