Protein and mRNA Studies of Rat FA1/Pref-1/dlk

Sammanfattning: The timing of cell differentiation is important for development and renewal of well functioning organs and tissues. One protein involved in this process is Preadipocyte factor 1 (Pref-1). Most likely, the role of this protein is to maintain cells in an undifferentiated state.The work presented in this thesis, has employed the rat as an animal model for the studies of Pref-1. Rat models of obesity (Zucker, ZO) and type II diabetes (Goto-Kakizaki, GK) were used to determine metabolic influence on Pref-1 and adipokine mRNA expression in adipose tissues.The Pref-1 cleavage product was purified from rat amniotic fluid and physicochemically characterised. Concentration of Pref-1 in serum, amniotic fluid and urine was determined by ELISA. Soluble Pref-1 and the compartmentalisation of the protein were highly similar to what had previously been demonstrated in mice and humans.Immunohistochemistry studies displayed similar staining patterns of Pref-1 in adrenal glands, ovaries and pituitary glands of non-pregnant and pregnant rats. This suggests that pregnancy do not influence the protein expression of Pref-1 in these organs.In the GK rats, Pref-1 mRNA was altered and a decrease in the visceral compared to subcutaneous adipose depots was demonstrated, in contrast to the ZO rats. Additionally, adiponectin, leptin, IL-6 and TNF-? mRNA levels were altered in the diabetic strain, indicating that this animal model expresses many of the typical features of type II diabetes.In conclusion, the rat is an appropriate model for studies of FA1/Pref-1/dlk. Pref-1 is highly elevated in fetal and maternal serum during pregnancy. However, the expression of Pref-1 in some endocrine tissues did not alter due to pregnancy. The mRNA expression of Pref-1 was altered between adipose depots and demonstrated to be affected by metabolic disturbances in the animals.