New research reveals that visceral adipose tissue helps maintain brain-derived neurotrophic factor (BDNF) levels, but this effect weakens with age, potentially contributing to cognitive decline.
A new study, led by Dr. Yoshinori Takei and Dr. Atsushi Sugiyama from Toho University’s Department of Pharmacology, along with Dr. Akira Hirasawa of Kyoto University’s Graduate School of Pharmaceutical Sciences and Dr. Yoko Amagase of Osaka Medical and Pharmaceutical University’s Faculty of Pharmacy, uncovers a novel link between visceral adipose tissue aging and brain health.
The findings were recently published in GeroScience, the official journal of the American Aging Association.
Key Points
- Visceral adipose tissue aids in maintaining the brain-derived neurotrophic factor (BDNF) level in the brain.
- The effects of the visceral adipose tissue on brain BDNF expression decrease with age.
- Some mechanisms corresponding to middle-aged weight gain appear to be involved in brain aging.
- The findings may contribute to the prevention and improvement of cognitive decline and depressive symptoms in older adults.
Research Overview
The research shows that the visceral adipose tissue, which stores fat in the peritoneal cavity, expresses the protein CX3CL1 to promote the 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 the 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.
Reference: “Adipose chemokine ligand CX3CL1 contributes to maintaining the hippocampal BDNF level, and the effect is attenuated in advanced age” by Yoshinori Takei, Yoko Amagase, Ai Goto, Ryuichi Kambayashi, Hiroko Izumi-Nakaseko, Akira Hirasawa and Atsushi Sugiyama, 13 February 2025, GeroScience.
DOI: 10.1007/s11357-025-01546-4
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