A new study led by Dr. Yoshinori Takei and Dr. Atsushi Sugiyama of the Department of Pharmacology, Faculty of Medicine, Toho University, along with Dr. Akira Hirasawa of the Graduate School of Pharmaceutical Sciences, Kyoto University, and Dr. Yoko Amagase of the Faculty of Pharmacy, Osaka Medical and Pharmaceutical University, reveals a novel connection between aging of visceral adipose tissue and brain health. These findings were published online on February 13, 2025, in GeroScience , the official journal of the American Aging Association.
Key Points :
Research Overview
The research shows that the visceral adipose tissue, which stores fat in the peritoneal cavity, expresses the protein CX3CL1 to promote production of BDNF, a critical molecule for maintaining cognitive function. In young mice, the adipose-to-brain crosstalk helps sustain cognitive health by ensuring adequate BDNF production. However, the crosstalk falters in aged mice, as CX3CL1 expression decreases in the adipose tissue with age. This age-related alteration potentially leads to cognitive decline, since brain BDNF is correlated to the cognition levels of older adults. Adjusting for the age-related decrease in peritoneal CX3CL1 has been shown to restore cognitive function impaired by aging.
Moreover, the research indicates that steroid hormones causing lipolysis in the adipose tissue promote CX3CL1 expression, and that the responsiveness of the tissue to steroid hormones declines in aged mice. Thus, in aged mice, insensitivity to steroid hormones appears to result in lower CX3CL1 production in the adipose tissue and a subsequent drop in BDNF levels in the brain. Since reduction of hormone-induced lipolysis is associated with abdominal fat accumulation in middle-age, the study suggests that the mechanism corresponding to middle-aged weight gain may also contribute to the age-related decline in brain BDNF.
These results open the door to new treatments aimed at preventing cognitive decline and alleviating depressive symptoms, ultimately enhancing the quality of life for older adults.
Published Journal
GeroScience (Published online: February 13, 2025)
Title
Adipose chemokine ligand CX3CL1 contributes to maintaining the hippocampal BDNF levels, and the effect is attenuated in advanced age
Authors
Yoshinori Takei*, Yoko Amagase, Ai Goto, Ryuichi Kambayashi, Hiroko Izumi Nakaseko, Akira Hirasawa and Atsushi Sugiyama*
DOI
10.1007/s11357-025-01546-4
GeroScience
Adipose chemokine ligand CX3CL1 contributes to maintaining the hippocampal BDNF level, and the effect is attenuated in advanced age
13-Feb-2025
The authors declare that they have no conflicts of interest.