Losing weight is often seen as the key to better health-but new research suggests that how the body reacts to weight loss may depend on when it happens in life. A groundbreaking study from Ben-Gurion University of the Negev (BGU) has uncovered that while midlife weight loss can successfully restore metabolic balance, it may also trigger temporary inflammation in the brain, raising new questions about how weight loss interacts with brain health as we age.
Obesity is a major global challenge, closely linked to diabetes, high blood pressure, and heart disease. Weight reduction through diet is known to reverse many of these risk factors. However, most studies focus on younger individuals, leaving an important question unanswered: how does the ageing body—and brain—adapt when weight loss happens later in life? To explore this, BGU scientists compared how young adult and middle-aged mice responded to diet-induced obesity followed by weight reduction.
Both age groups showed strong metabolic recovery, including improved blood glucose control, once their weight was reduced. But a striking difference emerged. Only the middle-aged mice developed increased inflammation in the hypothalamus—the brain region that regulates hunger, energy balance, and body temperature. Using advanced molecular assays and high-resolution imaging, the researchers detected activation of microglia, the immune cells of the brain, signaling a stress response that persisted for several weeks before fading.
While short-lived, this inflammation could have long-term implications. The hypothalamus plays a central role in maintaining metabolic and cognitive health, and prolonged inflammation has been associated with neurodegenerative diseases like Alzheimer’s.
According to Dr. Alexandra Tsitrina, the study provides a rare, multi-dimensional look at how structural and molecular mechanisms interact during weight loss. The team emphasizes that further research is needed to identify protective strategies that retain the metabolic advantages without taxing the brain.
This study reshapes how we view midlife health journeys—showing that while weight loss remains vital, its effects on the ageing brain deserve equal attention in the pursuit of lifelong wellbeing.
REFERENCE: Alon Zemer, Yulia Haim, Alexandra Tsitrina, Vered Chalifa-Caspi, Habib Muallem, Yair Pincu, G. William Wong, Uri Yoel, Alon Monsonego, Assaf Rudich. Weight loss aggravates obesity-induced hypothalamic inflammation in mid-aged mice. GeroScience, 2025; DOI: 10.1007/s11357-025-01933-x
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