Time-restricted feeding prevents memory impairments induced by obesogenic diet consumption in mice, in part through hippocampal thyroid hormone signaling.

Abstract

The consumption of calorie-rich diet has adverse effects on short and long-term memory, especially when introduced early in life when the brain is still maturing. Time-restricted feeding (TRF) without calorie restriction has proven to be an efficient strategy to reduce the deleterious effects of diet-induced obesity on metabolism. TRF was also shown to be beneficial to restore long-term memory in Alzheimer rodent models. Here, we provide evidence that four weeks of TRF restore the rhythmicity of some metabolic parameters together with short and long-term memory in mice fed a high fat-high sucrose (HFS) diet since weaning. Hippocampal translatome analyses indicated that impaired memory of mice under ad libitum HFS diet is accompanied by changes in genes associated with thyroid hormone signaling and astrocytic genes involved in the regulation of glutamate neurotransmission. TRF restored the diurnal expression variation of part of these genes and intra-hippocampal infusion of T3, the active form of thyroid hormone, rescued the memory performances of ad libitum HFS diet-fed mice. Thus, TRF demonstrates positive effects on both metabolism and memory in mice fed an obesogenic diet, highlighting this nutritional approach as a powerful tool in addressing obesity and its related comorbidities in mice. The analogous time-restricted eating in humans is an easy to implement lifestyle intervention that should now be tested in obese adolescents with memory alterations.