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Far-Infrared Therapy Based on Graphene Ameliorates High-Fat Diet-Induced Anxiety-Like Behavior in Obese Mice via Alleviating Intestinal Barrier Damage and Neuroinflammation

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Abstract

The consumption of a high-fat diet (HFD) has been implicated in the etiology of obesity and various neuropsychiatric disturbances, including anxiety and depression. Compelling evidence suggests that far-infrared ray (FIR) possesses beneficial effects on emotional disorders. However, the efficacy of FIR therapy in addressing HFD-induced anxiety and the underlying mechanisms remain to be elucidated. Here, we postulate that FIR emitted from a graphene-based therapeutic device may mitigate HFD-induced anxiety behaviors. The graphene-FIR modify the gut microbiota in HFD-mice, particularly by an enriched abundance of beneficial bacteria Clostridiaceae and Erysipelotrichaceae, coupled with a diminution of harmful bacteria Lachnospiraceae, Anaerovoracaceae, Holdemania and Marvinbryantia. Graphene-FIR also improved intestinal barrier function, as evidenced by the augmented expression of the tight junction protein occludin and G protein-coupled receptor 43 (GPR43). In serum level, we observed the decreased free fatty acids (FFA), lipopolysaccharides (LPS), diamine oxidase (DAO) and D-lactate, and increased the glucagon-like peptide-2 (GLP-2) levels in graphene-FIR mice. Simultaneously, inflammatory cytokines IL-6, IL-1β, and TNF-α manifested a decrease subsequent to graphene-FIR treatment in both peripheral and central system. Notably, graphene-FIR inhibited over expression of astrocytes and microglia. We further noticed that the elevated the BDNF and decreased TLR4 and NF-κB expression in graphene-FIR group. Overall, our study reveals that graphene-FIR rescued HFD-induced anxiety via improving the intestine permeability and the integrity of blood–brain barrier, and reduced inflammatory response by down regulating TLR4/NF-κB inflammatory pathway.

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Data Availability

The datasets used and/or analyzed in the current study are available from the corresponding author upon reasonable request.

References

  1. Blüher M (2019) Obesity: global epidemiology and pathogenesis. Nat Rev Endocrinol 15(5):288–298. https://doi.org/10.1038/s41574-019-0176-8

    Article  PubMed  Google Scholar 

  2. Petersen C, Bell R, Klag KA et al (2019) T cell-mediated regulation of the microbiota protects against obesity. Science 365(6451):eaat9351. https://doi.org/10.1126/science.aat9351

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  3. Ljungberg T, Bondza E, Lethin C (2020) Evidence of the importance of dietary habits regarding depressive symptoms and depression. Int J Environ Res Public Health 17(5):1616. https://doi.org/10.3390/ijerph17051616

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  4. Masana MF, Tyrovolas S, Kolia N et al (2019) Dietary patterns and their association with anxiety symptoms among older adults: the ATTICA study. Nutrients 11(6):1250. https://doi.org/10.3390/nu11061250

    Article  PubMed  Google Scholar 

  5. Baker KD, Loughman A, Spencer SJ, Reichelt AC (2017) The impact of obesity and hypercaloric diet consumption on anxiety and emotional behavior across the lifespan. Neurosci Biobehav Rev 83:173–182. https://doi.org/10.1016/j.neubiorev.2017.10.014

    Article  PubMed  Google Scholar 

  6. Hao S, Dey A, Yu X, Stranahan AM (2016) Dietary obesity reversibly induces synaptic stripping by microglia and impairs hippocampal plasticity. Brain Behav Immun 51:230–239. https://doi.org/10.1016/j.bbi.2015.08.023

    Article  PubMed  Google Scholar 

  7. Christ A, Günther P, Lauterbach MAR et al (2018) Western diet triggers NLRP3-dependent innate immune reprogramming. Cell 172(1–2):162-175.e14. https://doi.org/10.1016/j.cell.2017.12.013

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  8. Kim H, Bartley GE, Young SA, Davis PA, Yokoyama W (2012) HPMC supplementation reduces abdominal fat content, intestinal permeability, inflammation, and insulin resistance in diet-induced obese mice. Mol Nutr Food Res 56(9):1464–1476. https://doi.org/10.1002/mnfr.201200082

    Article  CAS  PubMed  Google Scholar 

  9. Bruce-Keller AJ, Salbaum JM, Luo M et al (2015) Obese-type gut microbiota induce neurobehavioral changes in the absence of obesity. Biol Psychiat 77(7):607–615. https://doi.org/10.1016/j.biopsych.2014.07.012

    Article  PubMed  Google Scholar 

  10. Lama A, Pirozzi C, Severi I et al (2022) Palmitoylethanolamide dampens neuroinflammation and anxiety-like behavior in obese mice. Brain Behav Immun 102:110–123. https://doi.org/10.1016/j.bbi.2022.02.008

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  11. Spencer SJ, D’Angelo H, Soch A, Watkins LR, Maier SF, Barrientos RM (2017) High-fat diet and aging interact to produce neuroinflammation and impair hippocampal- and amygdalar-dependent memory. Neurobiol Aging 58:88–101. https://doi.org/10.1016/j.neurobiolaging.2017.06.014

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  12. Cavaliere G, Trinchese G, Penna E et al (2019) High-fat diet induces neuroinflammation and mitochondrial impairment in mice cerebral cortex and synaptic fraction. Front Cell Neurosci 13:509. https://doi.org/10.3389/fncel.2019.00509

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  13. Wen X, Zhang B, Wu B et al (2022) Signaling pathways in obesity: mechanisms and therapeutic interventions. Signal Transduct Target Ther 7(1):298. https://doi.org/10.1038/s41392-022-01149-x

    Article  PubMed  PubMed Central  Google Scholar 

  14. Shui S, Wang X, Chiang JY, Zheng L (2015) Far-infrared therapy for cardiovascular, autoimmune, and other chronic health problems: a systematic review. Exp Biol Med 240(10):1257–1265. https://doi.org/10.1177/1535370215573391

    Article  CAS  Google Scholar 

  15. Saltmarche AE, Naeser MA, Ho KF, Hamblin MR, Lim L (2017) Significant improvement in cognition in mild to moderately severe dementia cases treated with transcranial plus intranasal photobiomodulation: case series report. Photomed Laser Surg 35(8):432–441. https://doi.org/10.1089/pho.2016.4227

    Article  PubMed  PubMed Central  Google Scholar 

  16. Ramezani F, Neshasteh-Riz A, Ghadaksaz A, Fazeli SM, Janzadeh A, Hamblin MR (2022) Mechanistic aspects of photobiomodulation therapy in the nervous system. Lasers Med Sci 37(1):11–18. https://doi.org/10.1007/s10103-021-03277-2

    Article  PubMed  Google Scholar 

  17. Silva G, Ferraresi C, de Almeida RT et al (2018) Infrared photobiomodulation (PBM) therapy improves glucose metabolism and intracellular insulin pathway in adipose tissue of high-fat fed mice. Lasers Med Sci 33(3):559–571. https://doi.org/10.1007/s10103-017-2408-2

    Article  PubMed  Google Scholar 

  18. Vatansever F, Hamblin MR (2012) Far infrared radiation (FIR): its biological effects and medical applications. Photonics Lasers Med 4:255–266. https://doi.org/10.1515/plm-2012-0034

    Article  PubMed  PubMed Central  Google Scholar 

  19. Zhang Y, Guo ZB, Nie YM et al (2022) Self-organization formation of multicellular spheroids mediated by mechanically tunable hydrogel platform: toward revealing the synergy of chemo- and noninvasive photothermal therapy against colon microtumor. Macromol Biosci 22(4):e2100498. https://doi.org/10.1002/mabi.202100498

    Article  CAS  PubMed  Google Scholar 

  20. Honda K, Inoué S (1988) Sleep-enhancing effects of far-infrared radiation in rats. Int J Biometeorol 32(2):92–94. https://doi.org/10.1007/BF01044900

    Article  CAS  PubMed  Google Scholar 

  21. Chang Y, Liu YP, Liu CF (2009) The effect on serotonin and MDA levels in depressed patients with insomnia when far-infrared rays are applied to acupoints. Am J Chin Med 37(5):837–842. https://doi.org/10.1142/S0192415X09007272

    Article  CAS  PubMed  Google Scholar 

  22. Li Q, Peng J, Luo Y, Zhou J, Li T, Cao L, Peng S, Zuo Z, Wang Z (2022) Far infrared light irradiation enhances Aβ clearance via increased exocytotic microglial ATP and ameliorates cognitive deficit in Alzheimer’s disease-like mice. J Neuroinflammation 19(1):145. https://doi.org/10.1186/s12974-022-02521-y

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  23. Khan I, Pathan S, Li XA et al (2019) Far infrared radiation induces changes in gut microbiota and activates GPCRs in mice. J Adv Res 22:145–152. https://doi.org/10.1016/j.jare.2019.12.003

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  24. Sharma N, Shin EJ, Kim NH et al (2019) Protective potentials of far-infrared ray against neuropsychotoxic conditions. Neurochem Int 122:144–148. https://doi.org/10.1016/j.neuint.2018.11.019

    Article  CAS  PubMed  Google Scholar 

  25. Lan Y, Ma Z, Chang L et al (2023) Sea buckthorn polysaccharide ameliorates high-fat diet induced mice neuroinflammation and synaptic dysfunction via regulating gut dysbiosis. Int J Biol Macromol 236:123797. https://doi.org/10.1016/j.ijbiomac.2023.123797

    Article  CAS  PubMed  Google Scholar 

  26. Pan W, Zhao J, Wu J et al (2023) Dimethyl itaconate ameliorates cognitive impairment induced by a high-fat diet via the gut-brain axis in mice. Microbiome 11(1):30. https://doi.org/10.1186/s40168-023-01471-8

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  27. Duan C, Huang L, Zhang C et al (2021) Gut commensal-derived butyrate reverses obesity-induced social deficits and anxiety-like behaviors via regulation of microglial homeostasis. Eur J Pharmacol 908:174338. https://doi.org/10.1016/j.ejphar.2021.174338

    Article  CAS  PubMed  Google Scholar 

  28. Leonardi I, Gao IH, Lin WY et al (2022) Mucosal fungi promote gut barrier function and social behavior via type 17 immunity. Cell 185(5):831-846.e14. https://doi.org/10.1016/j.cell.2022.01.017

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  29. Yang Y, Wang B, Zhong Z, Chen H, Ding W, Hoi MPM (2021) Clonazepam attenuates neurobehavioral abnormalities in offspring exposed to maternal immune activation by enhancing GABAergic neurotransmission. Biochem Pharmacol 192:114711. https://doi.org/10.1016/j.bcp.2021.114711

    Article  CAS  PubMed  Google Scholar 

  30. Ma X, Xiao W, Li H et al (2021) Metformin restores hippocampal neurogenesis and learning and memory via regulating gut microbiota in the obese mouse model. Brain Behav Immun 95:68–83. https://doi.org/10.1016/j.bbi.2021.02.011

    Article  CAS  PubMed  Google Scholar 

  31. Shi H, Ge X, Ma X et al (2021) A fiber-deprived diet causes cognitive impairment and hippocampal microglia-mediated synaptic loss through the gut microbiota and metabolites. Microbiome 9(1):223. https://doi.org/10.1186/s40168-021-01172-0

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  32. Heymsfield SB, Wadden TA (2017) Mechanisms, pathophysiology, and management of obesity. N Engl J Med 376(3):254–266. https://doi.org/10.1056/NEJMra1514009

    Article  CAS  PubMed  Google Scholar 

  33. Mero A, Tornberg J, Mäntykoski M, Puurtinen R (2015) Effects of far-infrared sauna bathing on recovery from strength and endurance training sessions in men. Springerplus 4:321. https://doi.org/10.1186/s40064-015-1093-5

    Article  PubMed  PubMed Central  Google Scholar 

  34. Hsu YH, Chen YC, Chen YW, Chiu TH, Kuo YT, Chen CH (2020) Far-infrared radiation prevents decline in β-cell mass and function in diabetic mice via the mitochondria-mediated Sirtuin1 pathway. Metabolism 104:154143. https://doi.org/10.1016/j.metabol.2020.154143

    Article  CAS  PubMed  Google Scholar 

  35. Wu H, Lv W, Pan Q et al (2019) Simvastatin therapy in adolescent mice attenuates HFD-induced depression-like behavior by reducing hippocampal neuroinflammation. J Affect Disord 243:83–95. https://doi.org/10.1016/j.jad.2018.09.022

    Article  CAS  PubMed  Google Scholar 

  36. Yang Y, Zhong Z, Wang B, Wang Y (2022) Xiaoyao San ameliorates high-fat diet-induced anxiety and depression via regulating gut microbiota in mice. Biomed Pharmacother 156:113902. https://doi.org/10.1016/j.biopha.2022.113902

    Article  CAS  PubMed  Google Scholar 

  37. Wang T, Han J, Dai H et al (2022) Polysaccharides from Lyophyllum decastes reduce obesity by altering gut microbiota and increasing energy expenditure. Carbohyd Polym 295:119862. https://doi.org/10.1016/j.carbpol.2022.119862

    Article  CAS  Google Scholar 

  38. Cani PD, Jordan BF (2018) Gut microbiota-mediated inflammation in obesity: a link with gastrointestinal cancer. Nat Rev Gastroenterol Hepatol 15(11):671–682. https://doi.org/10.1038/s41575-018-0025-6

    Article  CAS  PubMed  Google Scholar 

  39. Shin NR, Bose S, Choi Y et al (2021) Anti-obesity effect of fermented Panax notoginseng is mediated via modulation of appetite and gut microbial population. Front Pharmacol 12:665881. https://doi.org/10.3389/fphar.2021.665881

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  40. Takeuchi T, Kubota T, Nakanishi Y et al (2023) Gut microbial carbohydrate metabolism contributes to insulin resistance. Nature 621(7978):389–395. https://doi.org/10.1038/s41586-023-06466-x

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  41. Guo J, Cui G, Huang W et al (2023) Alterations in the human oral microbiota in systemic lupus erythematosus. J Transl Med 21(1):95. https://doi.org/10.1186/s12967-023-03892-3

    Article  PubMed  PubMed Central  Google Scholar 

  42. Dai Z, Li S, Meng Y et al (2022) Capsaicin ameliorates high-fat diet-induced atherosclerosis in ApoE-/- mice via remodeling gut microbiota. Nutrients 14(20):4334. https://doi.org/10.3390/nu14204334

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  43. Sun P, Wang M, Li Z et al (2022) Eucommiae cortex polysaccharides mitigate obesogenic diet-induced cognitive and social dysfunction via modulation of gut microbiota and tryptophan metabolism. Theranostics 12(8):3637–3655. https://doi.org/10.7150/thno.72756

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  44. Xue M, Ji X, Liang H et al (2018) The effect of fucoidan on intestinal flora and intestinal barrier function in rats with breast cancer. Food Funct 9(2):1214–1223. https://doi.org/10.1039/c7fo01677h

    Article  CAS  PubMed  Google Scholar 

  45. Dubé PE, Rowland KJ, Brubaker PL (2008) Glucagon-like peptide-2 activates beta-catenin signaling in the mouse intestinal crypt: role of insulin-like growth factor-I. Endocrinology 149(1):291–301. https://doi.org/10.1210/en.2007-0561

    Article  CAS  PubMed  Google Scholar 

  46. Zhang XY, Chen J, Yi K et al (2020) Phlorizin ameliorates obesity-associated endotoxemia and insulin resistance in high-fat diet-fed mice by targeting the gut microbiota and intestinal barrier integrity. Gut microbes 12(1):1–18. https://doi.org/10.1080/19490976.2020.1842990

    Article  CAS  PubMed  Google Scholar 

  47. Kim N, Lee J, Song HS et al (2022) Kimchi intake alleviates obesity-induced neuroinflammation by modulating the gut-brain axis. Food Res Int 158:111533. https://doi.org/10.1016/j.foodres.2022.111533

    Article  CAS  PubMed  Google Scholar 

  48. Crispino M, Trinchese G, Penna E, Cimmino F, Catapano A, Villano I, Perrone-Capano C, Mollica MP (2020) Interplay between peripheral and central inflammation in obesity-promoted disorders: the impact on synaptic mitochondrial functions. Int J Mol Sci 21(17):5964. https://doi.org/10.3390/ijms21175964

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  49. Zhao T, Zhan L, Zhou W et al (2021) The effects of Erchen decoction on gut microbiota and lipid metabolism disorders in Zucker diabetic fatty rats. Front Pharmacol 12:647529. https://doi.org/10.3389/fphar.2021.647529

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  50. Ogrodnik M, Zhu Y, Langhi LGP et al (2019) Obesity-induced cellular senescence drives anxiety and impairs neurogenesis. Cell Metab 29(5):1061-1077.e8. https://doi.org/10.1016/j.cmet.2018.12.008

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  51. Liu Q, Xi Y, Wang Q et al (2021) Mannan oligosaccharide attenuates cognitive and behavioral disorders in the 5xFAD Alzheimer’s disease mouse model via regulating the gut microbiota-brain axis. Brain Behav Immun 95:330–343. https://doi.org/10.1016/j.bbi.2021.04.005

    Article  CAS  PubMed  Google Scholar 

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Funding

This study was supported by Medical Special Cultivation Project of Anhui University of Science and Technology (NO. YZ2023H2C015) and the National Natural Science Foundation of China (NO. 81274117).

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Y.Z Z and Y. D designed the study. J.S Z, S. L, X. C, Y.L H, J.C L, Y. Z, R. X, H.J D and X.C T performed the experiments. J.S Z and S. L analyzed the data. X.X F provided the technical support. J.S Z and S. L wrote the manuscript. All authors contributed to the editorial changes in the manuscript. All the authors have read and approved the final version of the manuscript.

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Correspondence to Yun Deng or You-zhi Zhang.

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This study was approved by the Committee on the Ethics of Animal Experiments of the Academy of Military Medical Sciences. Approval number: IACUC-DWZX-2022-632. All the institutional and national guidelines for the care and use of laboratory animals were followed. Appropriate measures were taken to minimize the number and suffering of animals.

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Zhang, Js., Li, S., Cheng, X. et al. Far-Infrared Therapy Based on Graphene Ameliorates High-Fat Diet-Induced Anxiety-Like Behavior in Obese Mice via Alleviating Intestinal Barrier Damage and Neuroinflammation. Neurochem Res (2024). https://doi.org/10.1007/s11064-024-04133-9

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