Early maturational emergence of adult-like emotional reactivity and anxiety after brief exposure to an obesogenic diet

Vega-Torres, Julio David; Azadian, Matine; Rios-Orsini, Raul; Reyes-Rivera, Arsenio L.; Ontiveros-Angel, Perla; Figueroa, Johnny D.

doi:10.1101/2020.03.03.975789

Cited by 4 publications

(6 citation statements)

References 127 publications

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“…We have modeled this relationship by measuring stress reactivity to traumatic stress in a rat model of diet-induced obesity (DIO). Consistent with studies in obese adolescents, we reported that adolescent diet-induced obesity (DIO) in rats: 1) reduces hippocampal volume [12], 2) impairs the maturation of the corticolimbic fear circuits [13], 3) enhances behavioral vulnerabilities to psychosocial stress [12][13][14], and 4) results in profound fear extinction learning deficits [13,14], even in the absence of an obesogenic phenotype [15].…”

Section: Introductionsupporting

confidence: 67%

“…Obesity is highly comorbid with anxiety and stress-related disorders. Our studies indicate that consumption of an obesogenic WD during adolescence heightens stress reactivity, promotes anxiety-like behaviors, and impairs the structural integrity of neural substrates implicated in stress-induced psychopathology in rats [12][13][14][15]. Furthermore, there is support to the notion that impairments in brain and behavior can occur even in the absence of an obesogenic phenotype [13,[57][58][59][60][61][62][63]].…”

Section: Obesogenic Diets Trigger Redox Dysregulation and Neuroinflammentioning

confidence: 59%

“…The rats were given ad libitum access to water and either standard chow control diet (CD; 13% kcal fats and 53% kcal from carbohydrates; total density = 3.1 kcal; Harlan Laboratories Inc., Indianapolis, IN) or a Western-like high-saturated fat diet (WD; catalog #F6724; 41% kcal fats and 43% kcal from carbohydrates; total density = 4.6 kcal; Bio-Serv, Frenchtown, NJ). The composition of the diets is fully detailed in previous reports (Table 1) [13,15].…”

Section: Dietsmentioning

confidence: 99%

“…The fear-potentiated startle (FPS) protocol was adapted from Dr. Michael Davis [46] and detailed in previous studies from our laboratory [13][14][15]. Each FPS session started with a 5-min acclimation period (background noise = 55 dB).…”

Section: Fear Potentiated Startle (Fps)mentioning

confidence: 99%

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Oxidative Stress and Neuroinflammation in a Rat Model of Co-Morbid Obesity and Psychogenic Stress

Santana

Vega-Torres

Ontiveros-Angel

et al. 2020

Preprint

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Contributions: JMS, wrote manuscript, performed Western blot experiments and analyses; JDV, design and performed behavioral experiments, wrote manuscript; YAT, performed Western blot experiments; POA, performed and analyzed ELISA experiments, prepared illustrations, wrote manuscript; JBL, analyzed behavioral data; AYCG and EAB, performed Western blots; DZO and CAC, peformed Western blot analyses; JDF, planned experiments, analyzed data, wrote manuscript. AbstractBackground: There is growing recognition for a reciprocal, bidirectional link between anxiety disorders and obesity. Although the mechanisms linking obesity and anxiety remain speculative, this bidirectionality suggests shared pathophysiological processes. Neuroinflammation and oxidative damage are implicated in both pathological anxiety and obesity. This study investigates the relative contribution of comorbid dietinduced obesity and stress-induced anxiety to neuroinflammation and oxidative stress.Methods: Thirty-six (36) male Lewis rats were divided into four groups based on diet type and stress exposure: 1) control diet unexposed (CDU) and 2) exposed (CDE), 3)Western-like high-saturated fat diet unexposed (WDU) and 4) exposed (WDE).Neurobehavioral tests were performed to assess anxiety-like behaviors. The catalytic concentrations of glutathione peroxidase and reductase were measured from plasma samples, and neuroinflammatory/oxidative stress biomarkers were measured from brain samples using Western blot. Correlations between behavioral phenotypes and biomarkers were assessed with Pearson's correlation procedures. Results:We found that WDE rats exhibited markedly increased levels of glial fibrillary acidic protein (185%), catalase protein (215%), and glutathione reductase (GSR) enzymatic activity (418%) relative to CDU rats. Interestingly, the brain protein levels of glutathione peroxidase (GPx) and catalase were positively associated with body weight and behavioral indices of anxiety. Conclusions:Together, our results support a role for neuroinflammation and oxidative stress in heightened emotional reactivity to obesogenic environments and psychogenic stress. Uncovering adaptive responses to obesogenic environments characterized by 3 high access to high-saturated fat/high-sugar diets and toxic stress has the potential to strongly impact how we treat psychiatric disorders in at-risk populations. Highlights:• Predatory odor stress heightens footshock reactivity and anxiety-like behaviors in Lewis rats.• WD intake increases glutathione reductase activity in plasma.• WD intake and PS exposure acted synergistically to increase the brain protein levels of catalase and the glial fibrillary acidic protein.• The protein levels and activities of some redox/neuroinflammatory biomarkers are closely associated with behavioral proxies related to fear and anxiety in rats. astrocytes use glycolysis for energy production and, as a consequence, have been associated with a higher generation of mitochondrial reactive oxygen species (ROS) [26].It is known that ROS accumula...

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Section: Introductionsupporting

confidence: 67%

Section: Obesogenic Diets Trigger Redox Dysregulation and Neuroinflammentioning

confidence: 59%

Section: Dietsmentioning

confidence: 99%

Section: Fear Potentiated Startle (Fps)mentioning

confidence: 99%

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Oxidative Stress and Neuroinflammation in a Rat Model of Co-Morbid Obesity and Psychogenic Stress

Santana

Vega-Torres

Ontiveros-Angel

et al. 2020

Preprint

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“…We would like to thank the staff at the animal care facility. This manuscript has been released as a preprint in bioRxiv ( Vega-Torres et al, 2020 ) as a significantly revised manuscript from another preprint listed in the same repository ( Vega-Torres et al, 2019 ).…”

mentioning

confidence: 99%

Adolescent Vulnerability to Heightened Emotional Reactivity and Anxiety After Brief Exposure to an Obesogenic Diet

et al. 2020

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Background: Emerging evidence demonstrates that diet-induced obesity disrupts corticolimbic circuits underlying emotional regulation. Studies directed at understanding how obesity alters brain and behavior are easily confounded by a myriad of complications related to obesity. This study investigated the early neurobiological stress response triggered by an obesogenic diet. Furthermore, this study directly determined the combined impact of a short-term obesogenic diet and adolescence on critical behavioral and molecular substrates implicated in emotion regulation and stress. Methods: Adolescent (postnatal day 31) or adult (postnatal day 81) Lewis rats were fed for 1 week with an experimental Western-like high-saturated fat diet (WD, 41% kcal from fat) or a matched control diet (CD, 13% kcal from fat). We used the acoustic fearpotentiated startle (FPS) paradigm to determine the effects of the WD on cued fear conditioning and fear extinction. We used c-Fos mapping to determine the functional influence of the diet and stress on corticolimbic circuits. Results: We report that 1-week WD consumption was sufficient to induce fear extinction deficits in adolescent rats, but not in adult rats. We identify fear-induced alterations in corticolimbic neuronal activation and demonstrate increased prefrontal cortex CRHR1 messenger RNA (mRNA) levels in the rats that consumed the WD. Conclusion: Our findings demonstrate that short-term consumption of an obesogenic diet during adolescence heightens behavioral and molecular vulnerabilities associated with risk for anxiety and stress-related disorders. Given that fear extinction promotes resilience and that fear extinction principles are the foundation of psychological treatments for posttraumatic stress disorder (PTSD), understanding how obesogenic environments interact with the adolescent period to affect the acquisition and expression of fear extinction memories is of tremendous clinical relevance.

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Short-term exposure to an obesogenic diet during adolescence elicits anxiety-related behavior and neuroinflammation: modulatory effects of exogenous neuregulin-1

et al. 2022

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Childhood obesity leads to hippocampal atrophy and altered cognition. However, the molecular mechanisms underlying these impairments are poorly understood. The neurotrophic factor neuregulin-1 (NRG1) and its cognate ErbB4 receptor play critical roles in hippocampal maturation and function. This study aimed to determine whether exogenous NRG1 administration reduces hippocampal abnormalities and neuroinflammation in rats exposed to an obesogenic Western-like diet (WD). Lewis rats were randomly divided into four groups (12 rats/group): (1) control diet+vehicle (CDV); (2) CD + NRG1 (CDN) (daily intraperitoneal injections: 5 μg/kg/day; between postnatal day, PND 21-PND 41); (3) WD + VEH (WDV); (4) WD + NRG1 (WDN). Neurobehavioral assessments were performed at PND 43–49. Brains were harvested for MRI and molecular analyses at PND 49. We found that NRG1 administration reduced hippocampal volume (7%) and attenuated hippocampal-dependent cued fear conditioning in CD rats (56%). NRG1 administration reduced PSD-95 protein expression (30%) and selectively reduced hippocampal cytokine levels (IL-33, GM-CSF, CCL-2, IFN-γ) while significantly impacting microglia morphology (increased span ratio and reduced circularity). WD rats exhibited reduced right hippocampal volume (7%), altered microglia morphology (reduced density and increased lacunarity), and increased levels of cytokines implicated in neuroinflammation (IL-1α, TNF-α, IL-6). Notably, NRG1 synergized with the WD to increase hippocampal ErbB4 phosphorylation and the tumor necrosis alpha converting enzyme (TACE/ADAM17) protein levels. Although the results did not provide sufficient evidence to conclude that exogenous NRG1 administration is beneficial to alleviate obesity-related outcomes in adolescent rats, we identified a potential novel interaction between obesogenic diet exposure and TACE/ADAM17-NRG1-ErbB4 signaling during hippocampal maturation. Our results indicate that supraoptimal ErbB4 activities may contribute to the abnormal hippocampal structure and cognitive vulnerabilities observed in obese individuals.

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Early maturational emergence of adult-like emotional reactivity and anxiety after brief exposure to an obesogenic diet

Cited by 4 publications

References 127 publications

Oxidative Stress and Neuroinflammation in a Rat Model of Co-Morbid Obesity and Psychogenic Stress

Oxidative Stress and Neuroinflammation in a Rat Model of Co-Morbid Obesity and Psychogenic Stress

Adolescent Vulnerability to Heightened Emotional Reactivity and Anxiety After Brief Exposure to an Obesogenic Diet

Short-term exposure to an obesogenic diet during adolescence elicits anxiety-related behavior and neuroinflammation: modulatory effects of exogenous neuregulin-1

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