No description available.

Thesis (Ph. D.)--University of Texas at Austin, 2000. / Vita. Includes bibliographical references (leaves 141-175). Available also in a digital version from Dissertation Abstracts.

Licentiatavhandling (sammanfattning) Karlstad : Karlstads universitet, 2009. / Härtill 2 uppsatser.

Obesity features increased accumulation of fat in the body and results in adverse health consequences, including type II diabetes mellitus and cardiovascular diseases. The global epidemic of obesity and lack of effective treatments call for the search of new anti-obesity medication. Activation of prostaglandin receptor subtype 4 (EP4) had been shown to produce potent anti-inflammatory effect and possibly induce brite adipocytes to increase energy expenditure, both of which can potentially ameliorate obesity. The purpose of this dissertation is to characterize the metabolic phenotypes of EP4 receptor in mice and to elucidate whether administration of CAY10580, a selective EP4 agonist, could protect against obesity and its related complications. The experiments were carried out on diet-induced obese mice and EP4 knockout mice. Anthropometric measurement, glucose and insulin tolerance test, indirect calorimetry, quantitative real-time PCR, plasma analytes measurement and histological studies were performed. The findings revealed that EP4 activation by CAY10580 prevented high-fat diet fed mice from becoming obese, but it did not exhibit a curative effect in reversing obesity in mice. Activation of EP4 by CAY10580 suppressed body weight gain and adiposity in high-fat diet fed mice by reducing the weight of epididymal, subcutaneous and peri-renal white adipose tissues, inter-scapular brown adipose tissue and liver. The lower adiposity resulted in improved glucose and insulin sensitivity and lower plasma leptin level. The cause of reduced adiposity by EP4 activation is not due to changes in energy intake, obligatory energy expenditure, locomotor activities, adaptive thermogenesis and lipolysis. EP4- mediated reduction in adiposity was characterized by smaller adipocyte size and greater proportion of small adipocytes in subcutaneous white adipose tissue. Furthermore, mice deficient in EP4 also showed reduced adiposity at epididymal, subcutaneous and peri-renal white adipose tissues, and inter-scapular brown adipose tissue. The reduced adiposity in EP4 deficient mice was associated with impaired cold intolerance. Taken together, EP4 activation is effective in preventing obesity and relieving obesity-associated glucose and insulin tolerance, and EP4 might play an essential role in adiposity maintenance through the modulation on adipocyte development. / published_or_final_version / Pharmacology and Pharmacy / Master / Master of Medical Sciences

Obesity is a rising global health burden. The accumulation of fat in the body is associated with metabolic syndrome, type 2 diabetes, cardiovascular disease, hypertension and cancer. Currently available anti-obesity medications are not effective and safe to meet the medical need for obesity management. Prostaglandin E receptor subtype 4 (EP4) is involved in the development of adipocytes, but the signaling in adipogenesis and the effect on the regulation of energy homeostasis is not clear to understand. Thus, EP4 receptor and its signaling pathway are interest for research. The purpose of this dissertation is to investigate the morphology and metabolic alteration in mice and to elucidate whether the lack of EP4 by administration of L-161,982, a selective EP4 antagonist, could influence lipid metabolism of the adipocytes in subcutaneous white adipose tissue. Our findings revealed that whether the mice were fed with normal or high-fat diet, EP4 has no significant influence on the adipocyte size in subcutaneous white adipose tissues. The lack of EP4 also showed no significant effect on the basal or stimulated lipolysis of subcutaneous white adipose tissue. However, EP4 deficiency reverses hepatic lipid storage in high-fat fed mice compared to those fed with normal diet. In conclusion, EP4 might be altered lipid metabolism in the liver, which is crucial in the management of obesity. Prospective studies are essential to investigate the effect of EP4 and its signaling pathway on adiposity and lipid metabolism in the liver. / published_or_final_version / Pharmacology and Pharmacy / Master / Master of Medical Sciences

No description available.

No description available.

A cloned metastatic variant of a murine tumor cell line, Lewis lung carcinoma (LLC(C3), was synchronized by double exposure to thymidine (5 x 10-4 M) at G1/S boundary. The effects of Prostaglandin (PG)E1, PGE2, PG synthetase inhibitors, and an analog of cAMP (dbut-cANP) on the life cycle of synchronized LLC(C3) cells were examined. When added to cells in G1 phase, PGE1 and dbut-cAMP enhanced 3H-thymidine uptake during S phase. Both of these agents suppressed S phase when they were added to cells entering S phase. The addition of PGE2 to LLC(C3) cells in G1 phase had no effect on S phase of the synchronized LLC(C3) cells. Prostaglandin E2 suppressed S phase when it was added at the beginning of S phase. A low concentration of PGE2 was more suppressive to S phase than was a high concentration. Indomethacin, an irreversible PG synthetase inhibitor, and piroxicam, a reversible PG synthetase inhibitor, suppressed S phase of synchronized LLC(C3) cells. These results suggest that prostaglandins can regulate the cell cycle of LLC(C3) cells through modulation of cAMP levels.

Thesis (M.S.)--Virginia Polytechnic Institute and State University, 1991. / Vita. Abstract. Includes bibliographical references (leaves 75-92). Also available via the Internet.

Thesis (M. Phil.)--University of Hong Kong, 2009. / Includes bibliographical references (leaves 92-109) Also available in print.