ArticlePloS one2016
Obesity Takes Its Toll on Visceral Pain: High-Fat Diet Induces Toll-Like Receptor 4-Dependent Visceral Hypersensitivity.
Article in PloS one, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 30 papers.
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Who cites it
30 citing papers in PubMed, 63 citations in OpenAlex.
- Whole-Blood Fatty Acid Phenotypes and Subsequent Quality-of-Life Changes Among Cancer Survivors.Nutrients · 2026Article
- Obesity Is Independently Associated With Increased Risk of Fecal Incontinence and Altered Rectal Sensitivity.The American journal of gastroenterology · 2025Article
- Time-restricted feeding modulates neuron-glial interactions and circadian rhythm in the spinal cord of male Wistar rats fed a high-fat diet.Spinal cord · 2025Article
- The influence of sex on neuroimmune communication, pain, and physiology.Biology of sex differences · 2024Review
- Pathology of pain and its implications for therapeutic interventions.Signal transduction and targeted therapy · 2024Review
- Obesity Is Associated with Altered Rectal Sensitivity in Chronic Constipation.Digestive diseases and sciences · 2024Article
- TT Genotype ofNutrients · 2023Article
- High-fat/high-sucrose diet worsens metabolic outcomes and widespread hypersensitivity following early-life stress exposure in female mice.American journal of physiology. Regulatory, integrative and comparative physiology · 2023Article
- The Stressed Gut: Region-specific Immune and Neuroplasticity Changes in Response to Chronic Psychosocial Stress.Journal of neurogastroenterology and motility · 2023Article
- Early life adverse exposures in irritable bowel syndrome: new insights and opportunities.Frontiers in pediatrics · 2023Review
- Maternal High-Energy Diet during Pregnancy and Lactation Impairs Neurogenesis and Alters the Behavior of Adult Offspring in a Phenotype-Dependent Manner.International journal of molecular sciences · 2022Article
- Pathophysiological Commonality Between Irritable Bowel Syndrome and Metabolic Syndrome: Role of Corticotropin-releasing Factor-Toll-like Receptor 4-Proinflammatory Cytokine Signaling.Journal of neurogastroenterology and motility · 2022Review
- Antitoxic Effects of Curcumin against Obesity-Induced Multi-Organs' Biochemical and Histopathological Abnormalities in an Animal Model.Evidence-based complementary and alternative medicine : eCAM · 2022Article
- Elevated dietary ω-6 polyunsaturated fatty acids induce reversible peripheral nerve dysfunction that exacerbates comorbid pain conditions.Nature metabolism · 2021Article
- Mapping of Microglial Brain Region, Sex and Age Heterogeneity in Obesity.International journal of molecular sciences · 2021Review
- Pain in the Developing Brain: Early Life Factors Alter Nociception and Neurobiological Function in Adolescent Rats.Cerebral cortex communications · 2021Article
- Maternal high-fat diet induces sex-specific changes to glucocorticoid and inflammatory signaling in response to corticosterone and lipopolysaccharide challenge in adult rat offspring.Journal of neuroinflammation · 2020Article
- Plant-derived oleanolic acid ameliorates markers of subclinical inflammation and innate immunity activation in diet-induced pre-diabetic rats.Therapeutic advances in endocrinology and metabolism · 2020Article
- Inhibition of TLR4 Induces M2 Microglial Polarization and Provides Neuroprotection via the NLRP3 Inflammasome in Alzheimer's Disease.Frontiers in neuroscience · 2020Article
- Role of the Prefrontal Cortex in Pain Processing.Molecular neurobiology · 2019Review
Corrections and comments
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Authors and funding
4 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Exposure to high-fat diet induces both, peripheral and central alterations in TLR4 expression. Moreover, functional TLR4 is required for the development of high-fat diet-induced obesity. Recently, central alterations in TLR4 expression have been associated with the modulation of visceral pain. However, it remains unknown whether there is a functional interaction between the role of TLR4 in diet-induced obesity and in visceral pain. In the present study we investigated the impact of long-term exposure to high-fat diet on visceral pain perception and on the levels of TLR4 and Cd11b (a microglial cell marker) protein expression in the prefrontal cortex (PFC) and hippocampus. Peripheral alterations in TLR4 were assessed following the stimulation of spleenocytes with the TLR4-agonist LPS. Finally, we evaluated the effect of blocking TLR4 on visceral nociception, by administering TAK-242, a selective TLR4-antagonist. Our results demonstrated that exposure to high-fat diet induced visceral hypersensitivity. In parallel, enhanced TLR4 expression and microglia activation were found in brain areas related to visceral pain, the PFC and the hippocampus. Likewise, peripheral TLR4 activity was increased following long-term exposure to high-fat diet, resulting in an increased level of pro-inflammatory cytokines. Finally, TLR4 blockage counteracted the hyperalgesic phenotype present in mice fed on high-fat diet. Our data reveal a role for TLR4 in visceral pain modulation in a model of diet-induced obesity, and point to TLR4 as a potential therapeutic target for the development of drugs to treat visceral hypersensitivity present in pathologies associated to fat diet consumption.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.