High fried food consumption impacts anxiety and depression due to lipid metabolism disturbance and neuroinflammation

Abstract

Western dietary patterns have been unfavorably linked with mental health. However, the long-term effects of habitual fried food consumption on anxiety and depression and underlying mechanisms remain unclear. Our population-based study with 140,728 people revealed that frequent fried food consumption, especially fried potato consumption, is strongly associated with 12% and 7% higher risk of anxiety and depression, respectively. The associations were more pronounced among male and younger consumers. Consistently, long-term exposure to acrylamide, a representative food processing contaminant in fried products, exacerbates scototaxis and thigmotaxis, and further impairs exploration ability and sociality of adult zebrafish, showing anxiety- and depressive-like behaviors. Moreover, treatment with acrylamide significantly down-regulates the gene expression of tjp2a related to the permeability of blood–brain barrier. Multiomics analysis showed that chronic exposure to acrylamide induces cerebral lipid metabolism disturbance and neuroinflammation. PPAR signaling pathway mediates acrylamide-induced lipid metabolism disorder in the brain of zebrafish. Especially, chronic exposure to acrylamide dysregulates sphingolipid and phospholipid metabolism, which plays important roles in the development of anxiety and depression symptoms. In addition, acrylamide promotes lipid peroxidation and oxidation stress, which participate in cerebral neuroinflammation. Acrylamide dramatically increases the markers of lipid peroxidation, including (±)5-HETE, 11(S)-HETE, 5-oxoETE, and up-regulates the expression of proinflammatory lipid mediators such as (±)12-HETE and 14(S)-HDHA, indicating elevated cerebral inflammatory status after chronic exposure to acrylamide. Together, these results both epidemiologically and mechanistically provide strong evidence to unravel the mechanism of acrylamide-triggered anxiety and depression, and highlight the significance of reducing fried food consumption for mental health.

Long-term intake of thermo-induced oxidized oil results in anxiety-like and depression-like behaviors: involvement of microglia and astrocytes

“…74 A 2023 study showed significant increases in concentrations of γ-aminobutyric acid (GABA) and glutamine (Gln) in the group exposed to alanamide (a hazard in fried foods), suggesting disruption of typical neurotransmitter metabolism in the zebrafish brain, which may promote anxiety and depressive symptoms in zebrafish. 20 Metabolomics analysis using UPLC/QTOF-MS in this study showed that glutamate and glutamine levels were significantly increased in the TIOO group compared with the control group, which was consistent with previous studies. Studies have shown that astrocytes have a certain anti-anxiety effect, but when the ATP signaling pathway is inhibited, this function will be lost.…”

“…The high starch content in French fries, when fried, produces acrylamide, which promotes lipid peroxidation and oxidative stress. 20 These factors are associated with brain nerve inflammation and damage to the blood–brain barrier. However, the direct effect of TIOO on nerve damage has not been studied yet.…”

Dietary lipoic acid alleviates autism-like behavior induced by acrylamide in adolescent mice: the potential involvement of the gut–brain axis

“…35 Furthermore, recent studies have proposed that chronic ACR exposure induces symptoms of anxiety and depression in zebrafish. 36,37 In our animal model, ACR exposure worsened stereotypes, impaired learning and memory, and induced autism-like behaviors. However, LA supplementation restored learning and memory functions and improved sociability.…”

Elevated body mass index in youth is associated with dysregulated surrogate markers of neural inhibition & excitation, and internetwork functional dysconnectivity

“…Dysregulation in these areas may underlie some of the cognitive deficits that are observed in those with higher weight, cognitive issues that could precipitate and/or exacerbate the development of severe psychiatric conditions (Wang et al, 2023). These novel findings demonstrate the neurophysiological impact of obesity during a key window of neurodevelopment.…”