Neurobiology of co-morbid stress and a western diet in mice: mitochondrial, proteomic and behavioral outcomes.
Level 5 - mechanism / opinion, no new human data
Bench and animal research without human clinical data
PubMed 42043687 · doi:10.1007/s11011-026-01855-3
What was done
Male C57Bl/6 mice were fed either a control diet (12% kcal fat, 65% carbohydrate, 23% protein) or a Western diet (32% kcal fat, 57% carbohydrate, 11% protein) for 20 weeks. A subset underwent chronic restraint stress (2 hours daily for 2 weeks). Researchers evaluated anxiety-like behavior, sucrose preference, metabolic measures, mitochondrial respiratory function, neurochemistry (BDNF, GABA, glutamate), and proteomics in the frontal cortex and hippocampus.
What was found
The abstract reports directional findings without exact numbers or statistical values. Chronic stress alone reduced body weight, frontal cortex BDNF, GABA, and mitochondrial respiration, while increasing frontal cortex glutamate and anxiety-like behavior. Western diet alone induced weight gain, insulin resistance, and reduced sucrose preference, without independently altering frontal cortex neurochemistry or respiratory function. Combining chronic stress with a Western diet induced both anxiety-like behavior and anhedonia, exacerbated reductions in frontal cortex GABA and hippocampal BDNF, altered mitochondrial respiration, and switched neuroprotective proteomic pathways such as chaperone-mediated autophagy, reelin, and EIF2 from activation to suppression.
Why it matters
This study outlines the cellular and neurochemical mechanisms through which hypercaloric diet and chronic restraint stress interact to impair brain mitochondrial function and behavioral outcomes in mice.
Limits
The study was conducted exclusively in male mice, limiting direct applicability to humans and leaving female sex-specific responses unassessed. The abstract does not report sample sizes (n), numerical data, effect sizes, or confidence intervals.
Cited by
- supports Chronic stress in animals damages brain mitochondria, reducing mitochondrial density and energy transformation capacity in specific brain areas.