Who is Who in the Adipose Organ : A look at the Heterogeneity of Adipocyte Biology

The increasing prevalence of obesity and related health complications, such as type 2 diabetes, cardiovascular disease and cancer, demands thorough investigation of the underlying processes. One of the key tissues investigated in this context is adipose tissue. It is becoming increasingly clear that adipose tissue is a very dynamic and heterogenic organ. This thesis provides an overview of various aspects of adipose biology that illustrate its heterogenic nature and describes my own scientific contributions to this field. We typically distinguish between thermogenic, energy-expending brown adipocytes and energy-storing white adipocytes that are located in anatomically distinct adipose depots. In addition, brite (or beige) adipocytes are functionally thermogenic, but are located among white adipocytes. Related to functional variation, adipocytes and adipose tissues display a wide range of morphological appearances. An additional property that illustrates the heterogeneity among adipose cells and depots is the variation of cellular responses to physiological cues, such as changes in diet or environmental temperature. Furthermore, the developmental origins of various adipose types display great heterogeneity, which may explain some of the functional and dynamic differences that are observed. In line with the complexity of developmental origins, molecular markers that were initially proposed to distinguish between brown, brite/beige and white adipose subtypes have added to the notion that the composition of the adipose organ is much more complex than has long been appreciated. My own work has contributed to the enhancement of our understanding of the heterogeneity of adipose subtypes. In particular, my findings related to marker gene expression patterns have led to increased appreciation of the complex nature of adipose gene expression patterns and the complications of translating results obtained in mice to humans. Some of my other contributions have increased the understanding of the differences and similarities in thermogenic adipose tissue functionality and dynamics. With cell culture studies, I have revealed new characteristics of pre-adipose cells from various depots that further add to the appreciation of the adipose heterogeneity. Overall, this thesis provides an overview of important characteristics of the adipose organ, illustrating its heterogenic nature. Realization of this heterogeneity is of importance in order to properly study the adipose organ to ultimately understand how the adipose organ can be therapeutically targeted to effectively treat adipose-related diseases.At the time of the doctoral defense, the following papers were unpublished and had a status as follows: Paper 3: Manuscript. Paper 7: Manuscript. Paper 8: Manuscript.