Midlife Weight Loss restored healthy metabolism in young and mid-aged mice, but a new study shows it also temporarily increases brain inflammation in mid-aged animals, raising concerns about how slimming down during midlife may affect brain health.
Weight loss is widely promoted to reduce the risks of obesity, including diabetes and heart disease. But new research from Ben-Gurion University of the Negev suggests the benefits of losing weight may differ with age, at least in mice.
In the study, published in the journal GeroScience, researchers compared young adult mice and mid-aged mice that became obese through diet and then lost weight. While both groups showed clear metabolic improvements, only the mid-aged mice experienced increased inflammation in a key brain region.
Study Shows Metabolic Gains Across Ages
Scientists found that weight loss restored healthy blood glucose control in both young and mid-aged mice. The improvement indicates that core metabolic systems can recover from obesity regardless of age, the researchers said.
“These results confirm that Midlife Weight Loss remains a powerful tool for correcting metabolic dysfunction,” said Alon Zemer, an M.D.-Ph.D. candidate at Ben-Gurion University and the study’s first author.
The findings reinforce long-standing evidence that reducing excess weight can reverse obesity-related metabolic damage. However, the researchers emphasized that metabolism was not the whole story.
When the team examined the brain, they observed a stark difference between the age groups that could not be explained by metabolic measures alone.
Midlife Weight Loss Triggers Brain Response
Midlife Weight Loss in mice led to increased inflammation in the hypothalamus, a brain region responsible for regulating appetite, energy balance, and other vital functions. This inflammation was identified through molecular analysis and microscopic imaging of microglia, the brain’s immune cells.
The inflammatory response persisted for several weeks before gradually subsiding, the researchers reported. Young adult mice did not show the same brain reaction after losing weight.
“Losing weight in midlife is not a simple copy-and-paste of what works in young adulthood,” Zemer said. “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.”
While the inflammation eventually declined, scientists cautioned that brain inflammation has been linked in other studies to memory problems and neurodegenerative diseases, including Alzheimer’s. The long-term consequences of the temporary inflammation observed in the mice remain unclear.
Researchers Call for Caution and Further Study
The researchers said the inflammatory response could be part of the brain’s adaptation to rapid metabolic change. It is possible, they noted, that this response even contributes to the metabolic improvements seen after weight loss.
“Our study characterizes the body’s adaptive response to Midlife Weight Loss through molecular and structural changes,” said Dr. Alexandra Tsitrina, a senior member of the research team. She explained that advanced microscopy and computational image analysis enabled scientists to detect subtle brain changes with potential health implications.
The study focused only on mice, and the authors stressed that the findings should not be directly applied to humans without further research. Still, they said the results highlight the need for a more nuanced understanding of weight loss during midlife.
Future studies will aim to determine why this brain inflammation occurs and how long it lasts. Researchers hope to identify strategies that preserve the metabolic benefits of weight loss while minimizing potential risks to brain health as people age.
The research was supported by internal funding from Ben-Gurion University, the U.S.-Israel Binational Science Foundation and the Israel Science Foundation.
