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Updated: Nov 13, 2025
Fat Preference: A Novel Model of Eating Behavior in Rats
Published on: June 27, 2014
High-fat diet during adulthood interacts with prenatal stress, affecting both brain inflammatory and neuroendocrine
Alessandra Berry1, Monica Mazzelli2,3, Chiara Musillo1,4
1Center for Behavioral Sciences and Mental Health, Istituto Superiore di Sanità, Rome, Italy.
Insights
Prenatal stress (PNS) primes male rats for metabolic disorders. Adult high-fat diet (HFD) exposure reveals how PNS interacts with metabolic challenges, affecting stress and mood pathways.
Area of Science:
- Neuroscience
- Endocrinology
- Psychiatry
Background:
- Prenatal stress (PNS) can program offspring, increasing vulnerability to mood and metabolic disorders later in life.
- Adult male rats exposed to PNS show heightened susceptibility to metabolic stressors like a high-fat diet (HFD).
Purpose of the Study:
- To investigate if PNS interacts with adult metabolic challenges to induce an inflammatory phenotype.
- To examine the expression of inflammatory, stress, and mood/metabolic regulators in key brain regions.
Main Methods:
- Assessed gene expression of inflammatory markers (Il-1β, Tnf-α, Il-6), stress mediators (Nr3c1, Fkbp5), and mood/metabolic regulators (Bdnf, Ghs-R) in the hippocampus, prefrontal cortex, and hypothalamus.
- Utilized a rat model with prenatal stress followed by an 8-week high-fat diet (HFD) in adulthood.
Main Results:
- PNS reduced brain-derived neurotrophic factor (Bdnf) and tumor necrosis factor-alpha (Tnf-α) expression, effects counteracted by adult HFD exposure.
- Both HFD and PNS modulated the expression of stress mediators Nr3c1 and Fkbp5, with Fkbp5 correlating with anxiety-like behavior.
Conclusions:
- PNS and adult metabolic challenges engage similar neuroendocrine pathways, offering mechanistic insight into the comorbidity of mood and metabolic disorders.
- These findings highlight the long-lasting impact of early-life stress on adult susceptibility to metabolic and emotional dysregulation.
Abstract:
Prenatal stress (PNS) affects foetal programming and, through an interaction with subsequent challenges, can increase vulnerability to mood and metabolic disorders. We have previously shown that, following PNS, adult male rats are characterized by increased vulnerability to a metabolic stressor experienced at adulthood (8-week-high-fat diet-HFD). In this study, we specifically assessed whether PNS might interact with an adult metabolic challenge to induce an inflammatory phenotype. Changes in the expression levels of inflammatory (Il-1β, Tnf-α, Il-6) and of stress response mediators (Nr3c1, Fkbp5) as well as of mood and metabolic regulators (Bdnf, Ghs-R) were investigated in the hippocampus, prefrontal cortex and hypothalamus, brain regions involved in the pathogenesis of depression and prone to inflammation in response to stress. Overall, PNS reduced the expression of Bdnf and Tnf-α, while HFD administered at adulthood counteracted this effect suggesting that PNS impinges upon the same pathways regulating responses to a metabolic challenge at adulthood. Furthermore, HFD and PNS affected the expression of both Nr3c1 and Fkbp5, two neuroendocrine mediators involved in the response to stress, metabolic challenges and in the modulation of the emotional profile (as shown by the correlation between Fkbp5 and the time spent in the open arms of the elevated plus-maze). Overall, these results indicate that the same metabolic and neuroendocrine effectors engaged by PNS are affected by metabolic challenges at adulthood, providing some mechanistic insight into the well-known comorbidity between mood and metabolic disorders.
