ArticleTranslational psychiatry2019
A high-fat diet promotes depression-like behavior in mice by suppressing hypothalamic PKA signaling.
Article in Translational psychiatry, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 60 papers.
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Who cites it
60 citing papers in PubMed, 127 citations in OpenAlex.
- Cognition at the core of metabolic syndrome: linking metabolic load to behavioural impairment in a longitudinal high-fat diet rat model.Brain, behavior, & immunity - health · 2026Article
- KBN2201 Attenuates High-Fat Diet-Induced Adipose Tissue Expansion and Body Weight Gain in Male Mice.International journal of molecular sciences · 2026Article
- Palmitic acid-induced autolysosomal dysfunction and lipotoxicity in neuroinflammation and neurodegeneration.Neural regeneration research · 2026Article
- Neural mechanisms linking Western diet consumption and cognitive impairment: a role for the vagus nerve.Clinical science (London, England : 1979) · 2026Review
- Redefining the timeline: a three-phase framework of hypothalamic microinflammation in metabolic disease.Reviews in endocrine & metabolic disorders · 2026Review
- Selection of appropriate reference genes in ApoeIBRO neuroscience reports · 2026Article
- Phosphodiesterase 4 regulates pyroptosis in subarachnoid hemorrhage.Neural regeneration research · 2026Article
- Diet-induced obesity impairs refeeding responses and downregulates lateral septal GLP-1R in male rats: an effect reversed by weight-loss treatment.Frontiers in pharmacology · 2026Article
- Association of altered plasma long-chain fatty acids with migraine-related disability: a clinical cross-sectional study.Frontiers in nutrition · 2026Article
- Life's essential 8 and non-alcoholic fatty liver disease: unmasking depressive symptoms' mediating role.European journal of medical research · 2025Article
- Liraglutide improves depressive and cognitive deficits in a high-fat diet rat model of obesity: the role of hippocampal autophagy and the PI3K/Akt/mTOR pathway.Psychopharmacology · 2025Article
- [Role of dysregulation brain lipid metabolism in depression].Zhong nan da xue xue bao. Yi xue ban = Journal of Central South University. Medical sciences · 2025Review
- Comparison of Anti-Obesity Effects of Ginger Extract Alone and Mixed with Long Pepper Extract.Biomedicines · 2025Article
- Comprehensive microarray analysis for the identification of therapeutic targets within HIF-1α signalling networks in diet-induced obesity via hypothalamic inflammation.Archives of endocrinology and metabolism · 2025Article
- Timing of standard chow exposure determines the variability of mouse phenotypic outcomes and gut microbiota profile.Lab animal · 2025Article
- Bangpungtongsung-san alleviates depressive-like behavior and metabolic disturbances in high-fat diet-induced obesity: mechanisms involving inflammation, CREB/BDNF signaling, and NMDA receptor modulation.Frontiers in pharmacology · 2025Article
- Regular exercise ameliorates high-fat diet-induced depressive-like behaviors by activating hippocampal neuronal autophagy and enhancing synaptic plasticity.Cell death & disease · 2024Article
- Association between 29 food groups of diet quality questionnaire and perceived stress in Chinese adults: a prospective study from China health and nutrition survey.BMC public health · 2024Article
- Effects of prenatal THC vapor exposure on body weight, glucose metabolism, and feeding behaviors in chow and high-fat diet fed rats.International journal of obesity (2005) · 2024Article
- Transcutaneous vagus nerve stimulation modulates depression-like phenotype induced by high-fat diet via P2X7R/NLRP3/IL-1β in the prefrontal cortex.CNS neuroscience & therapeutics · 2024Article
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Authors and funding
8 authors at 3 institutions in 2 countries.
Funding
Abstract
Obesity is associated with an increased risk of depression. The aim of the present study was to investigate whether obesity is a causative factor for the development of depression and what is the molecular pathway(s) that link these two disorders. Using lipidomic and transcriptomic methods, we identified a mechanism that links exposure to a high-fat diet (HFD) in mice with alterations in hypothalamic function that lead to depression. Consumption of an HFD selectively induced accumulation of palmitic acid in the hypothalamus, suppressed the 3', 5'-cyclic AMP (cAMP)/protein kinase A (PKA) signaling pathway, and increased the concentration of free fatty acid receptor 1 (FFAR1). Deficiency of phosphodiesterase 4A (PDE4A), an enzyme that degrades cAMP and modulates stimulatory regulative G protein (Gs)-coupled G protein-coupled receptor signaling, protected animals either from genetic- or dietary-induced depression phenotype. These findings suggest that dietary intake of saturated fats disrupts hypothalamic functions by suppressing cAMP/PKA signaling through activation of PDE4A. FFAR1 inhibition and/or an increase of cAMP signaling in the hypothalamus could offer potential therapeutic targets to counteract the effects of dietary or genetically induced obesity on depression.
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