Abstract
The aging process involves a decline in certain cognitive abilities. Cognitive aging progresses more quickly with obesity and more slowly with exercise and fasting. All of these conditions have strong impacts on white adipose tissue, which suggests that this tissue may play a pivotal role in the progression of cognitive aging. Brain-derived neurotrophic factor (BDNF), a neurotrophin indispensable for maintaining brain functions, becomes insufficient with age. Obesity also decreases the BDNF level in the hippocampus. This deficiency not only results in cognitive impairment but increases susceptibility to obesity. Both exercise and fasting increase the BDNF level in the hippocampus. Our study demonstrates that the chemokine ligand CX3CL1 in white adipose tissue is involved in the regulation of the BDNF level in the hippocampus. Aging reduces CX3CL1 expression, interfering with the mechanisms. Other studies have suggested that obesity increases adipose CX3CL1 expression; however, CX3CL1 augmented under obese condition may not contribute to the promotion of the BDNF level in the hippocampus. This suggests that the malfunction of the adipose CX3CL1-mediated mechanism could be involved in the downregulation of the hippocampus BDNF level under obese conditions. Studies have also suggested that the adipose CX3CL1-mediated mechanism appears to be involved in the exercise-induced promotion of BDNF expression in the hippocampus. Its involvement in the fasting-induced BDNF promotion is still unknown. Therefore, aging, obesity, and exercise appear to affect white adipose tissue to regulate the hippocampus BDNF level. While further studies are required to elucidate the precise role of the adipose CX3CL1-mediated regulation of BDNF expression, studies on white adipose tissue may provide new therapeutic targets for preventing age-associated cognitive decline.