Glucocorticoids, metabolic adaptations and recovery : studies in specific mouse models

Auvinen, H.E. (2013)

Doctoral Thesis

Today__s Western society and work promotes a sedentary lifestyle. This, coupled with high caloric food availability has increased obesity followed by an increased prevalence of the metabolic syndrome (MetS), type 2 diabetes (T2D) and cardiovascular diseases (CVD). Epidemiological data show a clear association between increased cortisol plasma levels, CVD and obesity, but animal models of the MetS are inconclusive with respect to whether the hypothalamus-pituitary-adrenal (HPA) axis is activated or not. It has remained unknown if, and to what extent HPA axis activity plays a pathogenic role in MetS development, and if the development of MetS changes it. In this thesis, we investigate high fat diet (HFD)-effect on the basal HPA axis activity and the effect of chronically elevated, exogenuously administered, corticosterone on MetS features as well as atherosclerosis development in spesific mouse models. From these studies we concluded that HFD reduces HPA axis activity where supraphysiological corticosterone levels worsen the features of MetS and the metabolic adaptations to a period of corticosterone excess in mice are long-lasting and may not completely recover to restore homeostasis. Futher more corticosteroid excess has both beneficial and harmful effects on cardiovascular risk factors that can be explained by their immunosuppressive and metabolic properties.

• Metabolic syndrome
• Hypothalamus-pituitary-adrenal axis
• High fat diet
• Mouse
• Atherosclerosis development
• Corticosterone
• Glucocorticoids

• All authors: Auvinen, H.E.
• Supervisor: Pereira Arias, A.M.; Rensen, P.C.N.
• Co-supervisor: Biermasz, N.R.
• Qualification: Doctor (dr.)
• Awarding Institution: Leiden University Medical Center (LUMC), Leiden University
• Date: 2013-05-23
• ISBN (print): 9789461822697