Losing weight in midlife may have a hidden brain cost

· ScienceDaily
Source:Ben-Gurion University of the Negev
Summary:Weight loss restored healthy metabolism in both young and mid-aged mice, but the brain told a different story. In mid-aged animals, slimming down actually worsened inflammation in a brain region tied to appetite and energy balance. While this inflammation eventually subsided, brain inflammation has been linked to cognitive decline and neurodegenerative disease. The results suggest that weight loss in midlife may not be as straightforward as once thought.
Weight loss may boost metabolism in midlife, but it could also quietly stress the brain. Credit: Shutterstock

Obesity remains one of the most serious health challenges worldwide, and weight loss is often encouraged as a way to lower the risks tied to excess weight. But growing research suggests that the effects of weight loss may change with age. During midlife, losing weight may not always produce the same health benefits seen in younger adults and in some cases, it may also influence brain health.

In a new study from Ben-Gurion University of the Negev (BGU), researchers examined how diet-induced obesity and later weight loss affected young adult mice compared with mid-aged mice. In both groups, weight loss successfully restored healthy blood glucose control, showing that key metabolic improvements occur regardless of age. However, the scientists also observed an unexpected difference. In mid-aged mice, weight loss led to increased inflammation in the hypothalamus, a part of the brain involved in regulating appetite, energy use, and other essential functions.

Brain Inflammation Raises New Questions

This increase in brain inflammation was detected at the molecular level and through detailed microscopic imaging of microglia (the brain's immune cells). The inflammatory response lasted for several weeks before gradually declining. While the long-term effects of this response are still unclear and may even play a role in achieving metabolic improvements, the findings raise important concerns. Persistent or poorly regulated inflammation in the brain has been linked to memory problems and neurodegenerative conditions such as Alzheimer's. As a result, the study highlights new questions about how weight loss during midlife may interact with brain health.

Researchers Urge a More Nuanced View of Midlife Weight Loss

"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."

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."

Next Steps for Protecting Brain Health

The research team stresses the importance of additional studies to better understand why this temporary but concerning brain inflammation occurs during midlife weight loss. Future work could help scientists develop approaches that maintain the metabolic advantages of weight loss while also protecting brain health as people age.

The study, titled, "Weight loss aggravates obesity-induced hypothalamic inflammation in mid-aged mice" was published in GeroScience and supported by an internal grant at BGU (with the Ilse Katz Institute of Nanoscale Science and Technology), and grants from theUS-Israel Binational Science Foundation (Grant no. 2021083) and the Israel Science Foundation (Grant No. 194/24).

Related Terms

Limbic systemThe limbic system is a group of interconnected brain structures that play a central role in emotion, memory, motivation, and behavior. It is located deep within the brain, beneath the cerebral cortex, and includes key regions such as the amygdala, hippocampus, hypothalamus, thalamus, and parts of the cingulate cortex. Though not a single anatomical unit, the limbic system functions as a coordinated network that helps link emotional states with physiological responses and conscious thought.Cognitive neuroscienceThe field of cognitive neuroscience concerns the scientific study of the neural mechanisms underlying cognition and is a branch of neuroscience. Cognitive neuroscience overlaps with cognitive psychology, and focuses on the neural substrates of mental processes and their behavioral manifestations. The boundaries between psychology, psychiatry and neuroscience have become quite blurred. Cognitive neuroscientists tend to have a background in experimental psychology, neurobiology, neurology, physics, and mathematics. Methods employed in cognitive neuroscience include psychophysical experiments, functional neuroimaging, electrophysiological studies of neural systems and, increasingly, cognitive genomics and behavioral genetics. Clinical studies in psychopathology in patients with cognitive deficits constitute an important aspect of cognitive neuroscience. The main theoretical approaches are computational neuroscience and the more traditional, descriptive cognitive psychology theories such as psychometrics.Healthy dietA healthy diet contains a balance of food groups and all the nutrients necessary to promote good health. Human nutrition is enormously complex and a healthy diet may vary widely according to an individual's genetic makeup, environment, and health. Healthy eating is the practice of making choices about what and/or how much one eats with the intention of improving or maintaining good health. Typically, this means following recommendations for a healthy diet. The concept of healthy eating is primarily a problem in rich countries where the lifestyle includes a modicum of outdoor physical activities, high but not always high-quality food consumption, and a trend towards industrially-produced foods instead of locally-sourced, locally-prepared meals.WorkaholicA workaholic is a person who is addicted to work. The term generally implies that the person enjoys their work; it can also imply that they simply feel compelled to do it. There is no generally accepted medical definition of such a condition, although some forms of stress, impulse control disorder, obsessive-compulsive personality disorder and obsessive-compulsive disorder can be work-related.