published_or_final_version / Medicine / Master / Master of Philosophy

published_or_final_version / Medicine / Master / Master of Philosophy

published_or_final_version / Pharmacology and Pharmacy / Doctoral / Doctor of Philosophy

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

The objective of this investigation was to identify the appropriate isotopic fractionation factor for total body water (TBW) from ²H₂O enrichment in respiratory water vapor (RW) compared to serum (S), then to use the RW technique to estimate absolute TBW volumes and TBW relative to fat-free body mass (FFB) in three age groups (prepubescent, PP, age = 5-10 y; young adult, YA, age = 22-39 y; older adult, OA age = 65-84 y) of healthy white males and females. The effects of analytical technique (infrared spectrophotometry, IR versus isotope-ratio mass spectrometry, IRMS) and ambient relative humidity on estimates of TBW were also investigated. The composition of the FFB was estimated using a multi-component statistical model (body density, TBW and bone mineral density), and the errors associated with the traditional two-component formula for percent fat from body density were calculated. Our results demonstrated a significant (p < 0.0001) ²H₂O fractionation effect of 0.971 ± 0.005 (mean ± SEM, n = 36) for TBW from RW compared to S. Analysis by IR and IRMS were highly correlated (R² =.999) but IR values were significantly (p < 0.001) higher than IRMS. Deuterium enrichment in RW samples collected at ambient RH (∼20%) was significantly higher (Δ = 20.2 ± 4.5 ppm, mean ± SEM, p < 0.0005) than in RW samples collected at 100% RH, roughly equivalent to a 1.2 L (3.2%) difference in TBW. Total body water relative to FFB mass (W/FFB) was lower (p < 0.01) in YA males (71.0 ± 1.0%) and females (70.2 ± 1.3%) than in PP (boys = 73.1 ± 1.6%; girls = 72.2 ± 1.4%, mean ± SD). In OA, W/FFB was higher (p < 0.05) than in YA (OAM = 72.6 ± 1.1%; OAF = 72.2 ± 1.4%). The density of the FFB was 1.0996 and 1.0839 g/ml in OAM and OAF, respectively. Percent fat from density plus TBW and BMD was lower than from density alone in all groups but YA males, where it was 2.4 percent fat higher. In PP, the Siri density formula resulted in an overestimate of 5.8 ± 2.6 percent fat (mean ± SD, range = 1.4 to 13.6%). In OA females, the density formula overestimated percent fat by 4.4 ± 2.8% (range = 0 to 10.4%). In conclusion, RW corrected for isotopic fractionation will provide acceptable estimates of TBW, although the effects of analytical technique and RH should be controlled. The existence of age-related differences in FFB composition causes errors when the two-component model is used to estimate percent fat in PP and OA females.

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No description available.

Thesis (M. Phil.)--University of Hong Kong, 2008. / Also available in print.

Thesis (M. Phil.)--University of Hong Kong, 2008. / Also available online.

Thesis (Ph. D.)--Cornell University, 1918. / "Author's abstract of this paper issued by the Bibliographic service, January 12." "Reprinted from the Journal of morphology, vol. 30, no. 2, March, 1918." Cornell Univ. Libr. Bibliography: p. 510-513.