Morphological and metabolic alternations in adipose tissue of EP4 deficient mice

Abstract

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.