High‐fat diet during adulthood interacts with prenatal stress, affecting both brain inflammatory and neuroendocrine markers in male rats

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.

Inflammatory Signatures of Maternal Obesity as Risk Factors for Neurodevelopmental Disorders: Role of Maternal Microbiota and Nutritional Intervention Strategies

“…Excessive BMI before and during pregnancy has been associated with insulin resistance and gestational diabetes and is more likely to result in life-threatening conditions (both for the mother and the offspring) such as pre-eclampsia [ 91 ]. Moreover, it has been related to perinatal morbidity and to an overall increased chance for the offspring to develop metabolic, cardiovascular, and mental health disorders throughout life [ 8 , 14 , 92 ]. To this regard, an interesting meta-analysis performed by Thangaratinam and co-workers suggests that dietary interventions are the most effective way to contrast maternal obesity.…”

“…OS and inflammation are main features of obesity and play a pivotal role in mediating the negative effects of this condition during pregnancy for both the mother and the offspring [ 8 , 92 , 161 ]. Indeed, a tight regulation of the redox balance and inflammatory processes, particularly during pregnancy, is crucial for a proper fetal development [ 14 , 162 ]. Moreover, OS has been reported to impair human placental amino acid uptake and increase Na+ permeability, directly affecting amino acid transporters [ 163 ].…”

“…Inflammation has recently obtained widespread attention as a likely mediating mechanism for its involvement in the pathophysiology of both obesity and mental disorders [ 13 ] and for the emerging role of inflammatory mediators as regulators of brain homeostasis and plasticity [ 14 , 15 , 16 ]. As a general mechanism, the expansion of adipose tissue observed in obese subjects is associated with increased size and number of adipocytes leading to adipocyte hypoxia, infiltration of leukocytes, inflammation and insulin resistance [ 17 , 18 , 19 ].…”

Hippocampal Glycerol-3-Phosphate Acyltransferases 4 and BDNF in the Progress of Obesity-Induced Depression

“…Obese mice experienced a decline in cognitive function after a long-term high-fat diet, accompanied by corresponding pathological changes in hippocampal neurons, which are closely related to the decline of BDNF levels in hippocampus. Recent studies have found that obesity can induce hippocampal inflammation and impairs emotion related to the hippocampus (21).…”

EJN stress, brain and behaviour special issue

“…One is certainly the timing of the stressful challenge and the context. Especially early in life exposure to adversity has lasting impacts on brain and behaviour (Čater & Majdič, 2021; Clinton et al, 2021; Roque et al, 2021; Wang et al, 2021), specifically also with regard to addiction and reward circuitry (Roque et al, 2021; Rudolph et al, 2020; Levis et al, 2021; Mooney‐Leber et al, 2021), pain responding (Melchior et al, 2021), epigenetic programming (Alyamani et al, 2021; Womersley et al, 2021), neuroinflammation (Friend et al, 2020; Marsland et al, 2021) and in interaction with the metabolic regulation (Berry et al, 2021). Beyond this, it is even unclear how ‘normative’ developmental experiences contribute to stress‐related behaviours (Farber et al, 2020), but it may be that broader environmental factors, such as access to green space, may contribute to resilience and reduced stress responding (Rojas‐Carvajal et al, 2021).…”