Effect of the p75 Neurotrophin Receptor on Glycemic Control of Obese Mice during Time-Restricted Feeding

ABSTRACT Circulating glucose regulates organismal energy homeostasis and is tightly controlled in response to feeding behavior. In overweight individuals, glucose homeostasis is often perturbed due to resistance to normal satiety signals, such as insulin and leptin, leading to type 2 diabetes and its attendant complications. An emerging dietary intervention, time-restricted feeding (TRF), aims to ameliorate the adverse metabolic consequences of obesity, however, its effectiveness on glucose control is uncertain. Here, we demonstrate that TRF is only transiently effective in reducing pre-meal serum glucose levels in obese mice lacking leptin. However, in Ob/Ob mice that also lack a gene known to suppress behavior associated with TRF, the p75 neurotrophin receptor (p75NTR), a sustained reduction of glucose levels is observed. These results suggest that the effectiveness of TRF on glycemic control can be enhanced with concurrent targeting of modulators of glucose homeostasis and TRF response.