From nonalcoholic fatty liver disease to neuroinflammation: the role of chronic systemic inflammation

Abbott NJ, Patabendige AA, Dolman DE, Yusof SR, Begley DJ (2010) Structure and function of the blood-brain barrier. Neurobiol Dis 37:13–25

CAS  PubMed  Google Scholar 

Amani M, Shokouhi G, Salari AA (2019) Minocycline prevents the development of depression-like behavior and hippocampal inflammation in a rat model of alzheimer’s disease. Psychopharmacology 236:1281–1292

CAS  PubMed  Google Scholar 

Anderer S (2025) ‘Semaglutide improves severe liver disease in phase 3 trial’. Jama 333:2134

Argaw AT, Asp L, Zhang J, Navrazhina K, Pham T, Mariani JN, Mahase S, Dutta DJ, Seto J, Kramer EG, Ferrara N, Sofroniew MV, John GR (2012) ‘Astrocyte-derived VEGF-A drives blood-brain barrier disruption in CNS inflammatory disease’. J Clin Invest 122: 2454–2468

Atiq A, Lee HJ, Khan A, Kang MH, Rehman IU, Ahmad R, Tahir M, Ali J, Choe K, Park JS, Kim MO (2023) ‘Vitamin E analog trolox attenuates MPTP-induced Parkinson’s disease in mice, mitigating oxidative stress, neuroinflammation, and motor Impairment’. Int J Mol Sci 24:9942

Baeta-Corral R, De la Fuente M, Giménez-Llort L (2023) Sex-dependent worsening of NMDA-induced responses, anxiety, hypercortisolemia, and organometry of early peripheral Immunoendocrine impairment in adult 3xTg-AD mice and their long-lasting ontogenic modulation by neonatal handling. Behav Brain Res 438:114189

CAS  PubMed  Google Scholar 

Balusu S, Van Wonterghem E, De Rycke R, Raemdonck K, Stremersch S, Gevaert K, Brkic M, Demeestere D, Vanhooren V, Hendrix A, Libert C, Vandenbroucke RE (2016) Identification of a novel mechanism of blood-brain communication during peripheral inflammation via choroid plexus-derived extracellular vesicles. EMBO Mol Med 8:1162–1183

CAS  PubMed  PubMed Central  Google Scholar 

Banks WA (2005) Blood-brain barrier transport of cytokines: a mechanism for neuropathology. Curr Pharm Des 11:973–984

CAS  PubMed  Google Scholar 

Berardo C, Di Pasqua LG, Cagna M, Richelmi P, Vairetti M, Ferrigno A (2020) ‘Nonalcoholic fatty liver disease and non-alcoholic steatohepatitis: current issues and future perspectives in preclinical and clinical research’. Int J Mol Sci 21:9646

Bettcher BM, Tansey MG, Dorothée G, Heneka MT (2021) Peripheral and central immune system crosstalk in alzheimer disease - a research prospectus. Nat Rev Neurol 17:689–701

PubMed  PubMed Central  Google Scholar 

Bordet R, Deplanque D (2020) Brain-liver axis: a new pathway for cognitive disorders related to hepatic fibrosis. Eur J Neurol 27:2111–2112

CAS  PubMed  Google Scholar 

Carvalho-Tavares J, Hickey MJ, Hutchison J, Michaud J, Sutcliffe IT, Kubes P (2000) A role for platelets and endothelial selectins in tumor necrosis factor-alpha-induced leukocyte recruitment in the brain microvasculature. Circ Res 87:1141–1148

CAS  PubMed  Google Scholar 

Chen J, Mao K, Yu H, Wen Y, She H, Zhang H, Liu L, Li M, Li W, Zou F (2021) p38-TFEB pathways promote microglia activation through inhibiting CMA-mediated NLRP3 degradation in parkinson’s disease. J Neuroinflammation 18:295

CAS  PubMed  PubMed Central  Google Scholar 

Chen S, Cao Z, Nandi A, Counts N, Jiao L, Prettner K, Kuhn M, Seligman B, Tortorice D, Vigo D, Wang C, Bloom DE (2024) The global macroeconomic burden of alzheimer’s disease and other dementias: estimates and projections for 152 countries or territories. Lancet Glob Health 12:e1534–e43

CAS  PubMed  Google Scholar 

Colognesi M, Gabbia D, De Martin S (2020) ‘Depression and cognitive impairment-extrahepatic manifestations of NAFLD and NASH’. Biomedicines 8:229

Craveiro V, Severo M, Ramos E (2025) Association between adiposity distribution and low-grade systemic inflammation: tackling multicollinearity. Nutrition 135:112737

PubMed  Google Scholar 

Cui Y, Zhi SM, Ding PF, Zhu T, Chen XX, Liu XZ, Sheng B, Li XJ, Wang J, Zhang JT, Xu MX, Jiang YX, Hang CH, Li W (2025) Silybin attenuates microglia-mediated neuroinflammation via Inhibition of STING in experimental subarachnoid hemorrhage. Int Immunopharmacol 151:114305

CAS  PubMed  Google Scholar 

D’Mello C, Swain MG (2011) Liver-brain inflammation axis. Am J Physiol Gastrointest Liver Physiol 301:G749–G761

PubMed  Google Scholar 

D’Mello C, Swain MG (2014) Liver-brain interactions in inflammatory liver diseases: implications for fatigue and mood disorders. Brain Behav Immun 35:9–20

PubMed  Google Scholar 

D’Mello C, Le T, Swain MG (2009) Cerebral microglia recruit monocytes into the brain in response to tumor necrosis factoralpha signaling during peripheral organ inflammation. J Neurosci 29:2089–2102

PubMed  PubMed Central  Google Scholar 

Dantzer R, O’Connor JC, Freund GG, Johnson RW, Kelley KW (2008) From inflammation to sickness and depression: when the immune system subjugates the brain. Nat Rev Neurosci 9:46–56

CAS  PubMed  PubMed Central  Google Scholar 

Dhanda S, Gupta S, Halder A, Sunkaria A, Sandhir R (2018) Systemic inflammation without gliosis mediates cognitive deficits through impaired BDNF expression in bile duct ligation model of hepatic encephalopathy. Brain Behav Immun 70:214–232

CAS  PubMed  Google Scholar 

Di Vincenzo F, Del Gaudio A, Petito V, Lopetuso LR, Scaldaferri F (2024) Gut microbiota, intestinal permeability, and systemic inflammation: a narrative review. Intern Emerg Med 19:275–293

PubMed  Google Scholar 

Estrada LD, Ahumada P, Cabrera D, Arab JP (2019) Liver dysfunction as a novel player in alzheimer’s progression: looking outside the brain. Front Aging Neurosci 11:174

CAS  PubMed  PubMed Central  Google Scholar 

Gangopadhyay A, Ibrahim R, Theberge K, May M, Houseknecht KL (2022) Non-alcoholic fatty liver disease (NAFLD) and mental illness: mechanisms linking mood, metabolism and medicines. Front Neurosci 16:1042442

PubMed  PubMed Central  Google Scholar 

Gehrke N, Schattenberg JM (2020) Metabolic Inflammation-A role for hepatic inflammatory pathways as drivers of comorbidities in nonalcoholic fatty liver disease?? Gastroenterology 158:1929–1947.e6

CAS  PubMed  Google Scholar 

Ghanim H, Aljada A, Hofmeyer D, Syed T, Mohanty P, Dandona P (2004) Circulating mononuclear cells in the obese are in a Proinflammatory state. Circulation 110:1564–1571

CAS  PubMed  Google Scholar 

Ghersi-Egea JF, Strazielle N, Catala M, Silva-Vargas V, Doetsch F, Engelhardt B (2018) Molecular anatomy and functions of the choroidal blood-cerebrospinal fluid barrier in health and disease. Acta Neuropathol 135:337–361

CAS  PubMed  Google Scholar 

Global (2019) Regional, and National burden of alzheimer’s disease and other dementias, 1990–2016: a systematic analysis for the global burden of disease study 2016. Lancet Neurol 18:88–106

Google Scholar 

Gorlé N, Blaecher C, Bauwens E, Vandendriessche C, Balusu S, Vandewalle J, Van Cauwenberghe C, Van Wonterghem E, Van Imschoot G, Liu C, Ducatelle R, Libert C, Haesebrouck F, Smet A, Vandenbroucke RE (2018) The choroid plexus epithelium as a novel player in the stomach-brain axis during Helicobacter infection. Brain Behav Immun 69:35–47

PubMed  Google Scholar 

Graff E, Vedantam S, Parianos M, Khakoo N, Beiling M, Pearlman M (2023) Dietary intake and systemic inflammation: can we use food as medicine?? Curr Nutr Rep 12:247–254

PubMed  Google Scholar 

Guarner V, Rubio-Ruiz ME (2015) Low-grade systemic inflammation connects aging, metabolic syndrome and cardiovascular disease. Interdiscip Top Gerontol 40:99–106

PubMed  Google Scholar 

Haj-Mirzaian A, Amiri S, Amini-Khoei H, Hosseini MJ, Haj-Mirzaian A, Momeny M, Rahimi-Balaei M, Dehpour AR (2017) Anxiety- and Depressive-Like behaviors are associated with altered hippocampal energy and inflammatory status in a mouse model of crohn’s disease. Neuroscience 366:124–137

CAS  PubMed  Google Scholar 

Haruwaka K, Ikegami A, Tachibana Y, Ohno N, Konishi H, Hashimoto A, Matsumoto M, Kato D, Ono R, Kiyama H, Moorhouse AJ, Nabekura J, Wake H (2019) Dual microglia effects on blood brain barrier permeability induced by systemic inflammation. Nat Commun 10:5816

CAS  PubMed  PubMed Central  Google Scholar 

Haukeland JW, Damås JK, Konopski Z, Løberg EM, Haaland T, Goverud I, Torjesen PA, Birkeland K, Bjøro K, Aukrust P (2006) Systemic inflammation in nonalcoholic fatty liver disease is characterized by elevated levels of CCL2. J Hepatol 44:1167–1174

CAS  PubMed  Google Scholar 

Heneka MT, Kummer MP, Latz E (2014) Innate immune activation in neurodegenerative disease. Nat Rev Immunol 14:463–477

CAS  PubMed  Google Scholar 

Hoogland IC, Houbolt C, van Westerloo DJ, van Gool WA, van de Beek D (2015) Systemic inflammation and microglial activation: systematic review of animal experiments. J Neuroinflammation 12:114

PubMed  PubMed Central  Google Scholar 

Hoti G, Matencio A, Rubin Pedrazzo A, Cecone C, Appleton SL, Khazaei Monfared Y, Caldera F, Trotta F (2022) ‘Nutraceutical concepts and dextrin-based delivery systems’. Int J Mol Sci 23:4102

Huang X, Hussain B, Chang J (2021) Peripheral inflammation and blood-brain barrier disruption: effects and mechanisms. CNS Neurosci Ther 27:36–47

CAS  PubMed  Google Scholar 

Jawad MY, Meshkat S, Tabassum A, McKenzie A, Di Vincenzo JD, Guo Z, Musavi NB, Phan L, Ceban F, Kwan AT, Ramachandra R, Le GH, Mansur RB, Rosenblat JD, Ho R, Rhee TG, McIntyre RS (2023) ‘The bidirectional association of nonalcoholic fatty liver disease with depression, bipolar disorder, and schizophrenia’. CNS Spectr 28: 541–560

Jurcau A, Andronie-Cioara FL, Nistor-Cseppento DC, Pascalau N, Rus M, Vasca E, Jurcau MC (2023) ‘The involvement of neuroinflammation in the onset and progression of Parkinson’s Disease’. Int J Mol Sci 24:14582

Kim HS, Suh YH (2009) Minocycline and neurodegenerative diseases. Behav Brain Res 196:168–179

CAS  PubMed  Google Scholar 

Kjærgaard K, Daugaard Mikkelsen AC, Landau AM, Eriksen PL, Hamilton-Dutoit S, Magnusson NE, Thomsen MB, Chen F, Vilstrup H, Mookerjee RP, Bay-Richter C, Thomsen KL (2024) Cognitive dysfunction in early experimental metabolic dysfunction-associated steatotic liver disease is associated with systemic inflammation and neuroinflammation. JHEP Rep 6:100992

PubMed  Google Scholar 

Knight JM, Costanzo ES, Singh S, Yin Z, Szabo A, Pawar DS, Hillard CJ, Rizzo JD, D’Souza A, Pasquini M, Coe CL, Irwin MR, Raison CL, Drobyski WR (2021) ‘The IL-6 antagonist tocilizumab is associated with worse depression and related symptoms in the medically ill’. Transl Psychiatry 11: 58

Liddelow SA, Guttenplan KA, Clarke LE, Bennett FC, Bohlen CJ, Schirmer L, Bennett ML, Münch AE, Chung WS, Peterson TC, Wilton DK, Frouin A, Napier BA, Panicker N, Kumar M, Buckwalter MS, Rowitch DH, Dawson VL, Dawson TM, Stevens B, Barres BA (2017) Neurotoxic reactive astrocytes are induced by activated microglia’. Nature 541: 481– 87

Linnerbauer M, Wheeler MA, Quintana FJ (2020) Astrocyte Cro

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