A study in mice reveals that weight loss in midlife can trigger temporary brain inflammation, even as metabolic health improves. Credit: Shutterstock
Emerging research suggests that weight loss in midlife may affect the brain differently than in young adulthood.
Obesity remains one of the most significant health challenges worldwide, and losing weight is often encouraged to lower the risks linked to the condition. Growing research, however, suggests that weight loss during midlife may not provide the same advantages seen in younger individuals and in some situations, it could influence brain health in unexpected ways.
A recent investigation by scientists at Ben-Gurion University of the Negev (BGU) examined how diet-induced obesity and later weight loss affected young adult and mid-aged mice. Both groups regained healthy blood glucose control during the weight-loss phase, indicating that key metabolic improvements can occur at different ages. Yet in mid-aged mice, the process of losing weight unexpectedly aggravated inflammation in the hypothalamus, a brain region that governs appetite, energy balance, and numerous essential functions.
A graphical abstract of the article. Credit: Prof. Assaf Rudich
The researchers found that this neuroinflammation, detected through molecular analysis and microscopic imaging of microglia (the brain’s immune cells), lasted for several weeks before gradually fading. The long-term impact of this heightened inflammatory response is still unclear, and it may even play a role in enabling the metabolic improvements seen during weight loss.
Even so, the results are cause for caution. Persistent or abnormal inflammation in the brain has been associated with cognitive decline and conditions such as Alzheimer’s disease. Because of this, the findings introduce important questions about how weight loss during midlife might influence overall brain health.
Scientists Call for Caution and Further Research
“Our findings show that losing weight in midlife is not a simple copy-and-paste of what works in young adulthood,” said Alon Zemer, an M.D.-Ph.D. candidate and the first author of this paper. “Weight loss remains essential for restoring metabolic health in obesity, but we need to understand the impact of weight loss on the mid-age brain and ensure brain health is not compromised.”
Left to right: Alon Zemer and Dr. Alexandra Tsitrina. Credit: Habib Muallem
Dr. Alexandra Tsitrina added: “Our study characterizes the body’s adaptive response to weight loss through two complementary dimensions – molecular and structural. This high-end imaging by advanced microscopy and image analysis with advanced computational analysis enable detection of sensitive changes with potential health ramifications.”
The researchers emphasize the need for further studies to uncover the mechanisms behind this temporary but concerning neuroinflammatory response. Future research may help design strategies that preserve the benefits of weight loss while safeguarding brain health in midlife and beyond.
Reference: “Weight loss aggravates obesity-induced hypothalamic inflammation in mid-aged mice” by Alon Zemer, Yulia Haim, Alexandra Tsitrina, Vered Chalifa-Caspi, Habib Muallem, Yair Pincu, G. William Wong, Uri Yoel, Alon Monsonego and Assaf Rudich, 17 October 2025, GeroScience.
DOI: 10.1007/s11357-025-01933-x
The study was supported by an internal grant at BGU (with the Ilse Katz Institute of Nanoscale Science and Technology), and grants from the US-Israel Binational Science Foundation (Grant no. 2021083) and the Israel Science Foundation (Grant No. 194/24).
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