Metabolism reaches far beyond the body
Not all fat is the same. While body weight has long been considered a key indicator of metabolic health, researchers are increasingly asking a more specific question: Where does the body store fat – and what does this mean for our health?
A new study by researchers from the Institute of Diabetes Research and Metabolic Diseases (IDM) of Helmholtz Munich at the University of Tübingen shows that the distribution of body fat is not only important for metabolic health but is also linked to changes in brain insulin responsiveness in a sex-specific manner.
The findings have been published in Diabetologia.
The hippocampus: a metabolism-related brain region
The hippocampus is well known for its role in learning and memory. However, this brain region is much more than a memory center: it also interacts closely with metabolic processes and responds to insulin.
Reduced sensitivity to insulin in the brain may disrupt communication between metabolism and the brain. Brain insulin resistance is increasingly recognized as a potential link between metabolic disorders and age-related changes in cognitive health.
Visceral fat and liver fat as metabolic warning signs
The researchers studied 260 adults without type 2 diabetes, combining advanced imaging techniques with detailed metabolic assessments.
The findings revealed that fat distribution matters in a sex-specific manner. Higher levels of visceral adipose tissue and liver fat were associated with reduced hippocampal insulin responsiveness.
These results highlight that metabolic health cannot be fully captured by body weight alone. The location of stored fat are crucial factors.
Women show stronger associations
One of the most striking findings was the difference between women and men.
Women with increasing age and unhealthy fat distribution showed a stronger decline in hippocampal insulin sensitivity. Women with increased metabolic risk also demonstrated reduced hippocampal insulin responses and the results differed between pre- and postmenopausal women.
These sex-specific differences provide new insights into why metabolic and brain health trajectories may differ between women and men across the lifespan.
Towards more personalized prevention strategies
The study deepens our understanding of the close relationship between metabolism and brain insulin responsiveness. It demonstrates that metabolic alterations may interact with the brain even without and long before the onset of diabetes.
The findings highlight the need for personalized prevention strategies that consider not only body weight and glucose levels, but also fat distribution, sex, and individual metabolic risk profiles.
Publication:
Sandforth L, Veit R, Machann J et al. Unhealthy fat distribution as a sex-specific predictor of declining hippocampus insulin sensitivity. Diabetologia (2026).
DOI: 10.1007/s00125-026-06787-2