Subcutaneous adipose tissue(SAT) acts as a metabolic sink storing excess fats safely and this process is initially facilitated by its increased expandability. There is a paucity of publication describing extracellular matrix(ECM) remodeling during SAT expansion and its comparison with other fat depots. Therefore, we undertook a longitudinal study in a high fat diet (HFD) mouse model investigating the changes in ECM, along with profibrotic, adipogenic, thermogenic and inflammatory markers genes in SAT, epididymal adipose tissue(EPI) and brown adipose tissue(BAT) depots.

Fat tissues from these depots in C57BL/6 mice were collected after 6 and 30 weeks of HFD and compared with age matched chow controls. At both 6 and 30 weeks mice fed HFD were heavier (2.5 fold) and fat pad mass increased(both >3.5  fold in SAT, both>2.1  fold in EPI and >2.0 fold in BAT at 30 weeks). Shown in Table 1 in SAT there were significant fold change increases in profibrotic and ECM remodeling markers but they were significantly decreased at 30 weeks. This is consistent with early higher ECM remodeling occurring in SAT to lodge increased flux of fats into new preadipocytes. This data was supported by increased adipogensis in SAT compared to EPI and BAT and a significantly higher mitochondrial thermogenic capacity facilitating the burning excess calories. By 30 weeks markers of adipogensis and thermogenesis were significantly decreased indicating impaired capacity in SAT to handle excessive fats safely. This shift in SAT capacity would facilitate fat deposition into other tissues and enhance EPI inflammation which was more pronounced than in the other fat depots at week 30.

We hypothesize that SAT accommodates excessive fats through increased ECM remodeling, increased adipogenesis and mitochondrial thermogensis. This appears to be a saturable process which when exceeded leads to accumulation of excess fat in EPI and other ectopic tissue.