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Reduced levels of white adipocyte hormone adiponectin have been observed in obese individuals with type 2 diabetes (T2D). Higher adiponectin levels are monotonically associated with a lower risk of T2D and hence increasing circulating adiponectin levels is of great interest in diabetic research. A novel compound, called fibroblast growth factor 21 (FGF21), is showing great potential in treatment of obesity and T2D. In animal models with obesity and T2D FGF21 increases glucose uptake, improves lipid homeostasis, decreases fat mass and increases circulating adiponectin levels. In this study, theaim is to explore the acute effect of FGF21 on white adipocyte adiponectin secretion. Adiponectinsecretion experiments were performed on primary murine adipocytes incubated with FGF21 for 30minutes and adiponectin levels were measured with ELISA and normalised to total protein content.To study the signalling pathway of FGF21, a separate batch of murine adipocytes were pretreated with an Epac and PI3K inhibitor prior to addition of FGF21. Results from this thesis show that FGF21potently stimulates short-term adiponectin release via PI3K-dependent pathways with no effect on adiponectin synthesis.

Endometrial adenocarcinoma is a cancer that develops from the endometrium, from cells thatform the glands in the endometrium. Animal models such as the BDII rat have thecharacteristic property that they are prone to cancers, characterized by rapid tumor growth,that resemble human cancers. Such rat models are therefore used to study gene expression andsignal pathways in cancer. Cancer cells have the ability to invade surrounding tissues throughlymphatic and/or vascular circulation to produce secondary tumors at new sites. TheRho/ROCK pathway orchestrates cell motility thereby contributing in significantly tometastasis. ROCK, through phosphorylation of myosin phosphatase target subunit 1(MYPT1), inhibits MYPT1 and induces actomyosin contraction which contributes to manycellular processes. In this study, we were interested in investigating the expression of MYPT1and ROCK1 genes in malignant and non-malignant endometrial cell lines in BDII rat model,in human endometrial cancer cells represented by the Ishikawa cells line, and in humanembryonic kidney 293 (HEK293) human non-malignant control cells. Although statisticalsignificance was not reached due to the small sample size, a difference in the gene expressionlevels in malignant and non-malignant cells was observed. The results from the present studyshowed a higher expression of MYPT1 and ROCK1 genes in cancer cells (rat and human)compared to non-cancer cells, and we can conclude that this implicates the significance of theMYPT1/ROCK pathway in endometrial cancer and its deregulation.

Pulmonary oedema and pulmonary hypertension are often associated with heart failure. The Balb/CJ and C57BL/6J mouse strains have been shown to exhibit distinct genetic susceptibilities to heart failure. Balb/CJ develops reduced heart function associated with pulmonary edema and pulmonary hypertension when treated with angiotensin II and a high-salt diet (ANG II + Salt) while C57BL/6J does not. The aim of this study was to investigate the effects of ANG II + Salt on lung damage by studying the potential immune cell infiltration in Balb/CJ mice and to determine whether differences in expression levels of angiotensin II type 1 and 2 (AT1 and AT2) receptors contribute to these effects. Protein expression of macrophages, neutrophils, AT1 receptors, and AT2 receptors in lung samples from six Balb/CJ mice and seven C57BL/6J mice treated with ANG II + Salt were analysed using Western blot. Five untreated mice from each strain were used as controls. The results indicated a significant difference (p=0.009) in the expression of macrophages between Balb/CJ mice treated with ANG II + Salt with a mean value of 17.30 and C57BL/6J mice treated with ANG II + Salt with a mean value of 9.34. No significant differences were observed in the expression of neutrophils, AT1 receptors, or AT2 receptors between the groups. Contrary to our expectations, the results did not support immune cell infiltration in Balb/CJ mice lungs or show higher AT1 receptor levels in Balb/CJ mice compared to C57BL/6J mice. Further research is required to understand the underlying mechanisms involved.

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