The host response to poly(lactide-co-glycolide) scaffolds protects mice from diet induced obesity and glucose intolerance

Underlying metabolic disease is poor adipose tissue function characterized by impaired glucose tolerance and low expression of health promoting adipokines. Currently, no treatments specifically target the adipose tissue and we are investigating polymer scaffolds for localized drug delivery as a therapeutic platform. In this work we implanted porous poly(lactide-co-glycolide) scaffolds into the epididymal fat of mice. Surprisingly, “empty” scaffolds decreased blood glucose levels in healthy mice as well as epididymal fat pad size. By injecting a fluorescent glucose tracer into mice, we determined that glucose uptake increases by 60% in epididymal fat pads with scaffolds; in contrast, glucose uptake was not elevated in other major metabolic organs, suggesting the enhanced glucose uptake at the scaffold implant site was responsible for decreased blood glucose levels. Histology indicated increased cellularity and tissue remodeling around the scaffold and we found increased expression of glucose transporter 1 and insulin-like growth factor 1, which are proteins involved in wound healing that can also modulate blood glucose levels through their promotion of glucose uptake. Regarding clinical translation, “empty” scaffolds decreased obesity and improved glucose tolerance in mice fed a high fat diet. These findings demonstrate increased cellular activity in the adipose tissue, such as that associated with the host response to biomaterial implant, is beneficial in mice suffering from metabolic complications of over nutrition, possibly because it mitigates the positive energy balance that leads to the obese, diabetic state. More broadly, this work reaffirms that in addition to the local host response typically investigated, biomaterial implant has systemic physiological effects and suggests that there may be implications for therapy.