The limited storage capacity of gonadal adipose tissue directs the development of metabolic disorders in male C57Bl/6J mice

Aims/hypothesis White adipose tissue (WAT) consists of various depots with different adipocyte functionality and immune cell composition. Knowledge of WAT-depot-specific differences in expandability and immune cell influx during the development of obesity is limited, therefore we aimed to characterise different WAT depots during the development of obesity in mice. Methods Gonadal WAT (gWAT), subcutaneous WAT (sWAT) and mesenteric WAT (mWAT) were isolated from male C57Bl/6J mice with different body weights (approximately 25-60 g) and analysed. Linear and non-linear regression models were used to describe the extent of WAT depot expandability and immune cell composition as a function of body weight. Results Whereas mouse sWAT and mWAT continued to expand with body weight, gWAT expanded mainly during the initial phase of body weight gain. The expansion diminished after the mice reached a body weight of around 40 g. From this point on, gWAT crown-like structure formation, liver steatosis and insulin resistance occurred. Mouse WAT depots showed major differences in immune cell composition: gWAT consisted mainly of macrophages, whereas sWAT and mWAT primarily contained lymphocytes. Conclusions/interpretation Marked inter-depot differences exist in WAT immune cell composition and expandability. The limited storage capacity of gWAT seems to direct the development of metabolic disorders in male C57Bl/6J mice.