Zheng Y, Ley SH, Hu FB. Global aetiology and epidemiology of type 2 diabetes mellitus and its complications. Nat Rev Endocrinol. 2018;14(2):88–98.
PubMed
Google Scholar
Arnold SE, et al. Brain insulin resistance in type 2 diabetes and Alzheimer disease: concepts and conundrums. Nat Rev Neurol. 2018;14(3):168–81.
CAS
PubMed
PubMed Central
Google Scholar
Milanski M, et al. Inhibition of hypothalamic inflammation reverses diet-induced insulin resistance in the liver. Diabetes. 2012;61(6):1455–62.
CAS
PubMed
PubMed Central
Google Scholar
Mu ZP, et al. Association between tumor necrosis factor-alpha and diabetic peripheral neuropathy in patients with type 2 diabetes: a meta-analysis. Mol Neurobiol. 2017;54(2):983–96.
CAS
PubMed
Google Scholar
Saltiel AR, Olefsky JM. Inflammatory mechanisms linking obesity and metabolic disease. J Clin Invest. 2017;127(1):1–4.
PubMed
PubMed Central
Google Scholar
Decourt B, Lahiri DK, Sabbagh MN. Targeting tumor necrosis factor alpha for Alzheimer’s disease. Curr Alzheimer Res. 2017;14(4):412–25.
CAS
PubMed
PubMed Central
Google Scholar
Orti-Casan N, et al. Targeting TNFR2 as a novel therapeutic strategy for Alzheimer’s disease. Front Neurosci. 2019;13:49.
PubMed
PubMed Central
Google Scholar
Harms AS, et al. Regulation of microglia effector functions by tumor necrosis factor signaling. Glia. 2012;60(2):189–202.
PubMed
Google Scholar
Zalevsky J, et al. Dominant-negative inhibitors of soluble TNF attenuate experimental arthritis without suppressing innate immunity to infection. J Immunol. 2007;179(3):1872–83.
CAS
PubMed
Google Scholar
McCoy MK, Tansey MG. TNF signaling inhibition in the CNS: implications for normal brain function and neurodegenerative disease. J Neuroinflammation. 2008;5:45.
PubMed
PubMed Central
Google Scholar
Peluso I, Palmery M. The relationship between body weight and inflammation: lesson from anti-TNF-alpha antibody therapy. Hum Immunol. 2016;77(1):47–53.
CAS
PubMed
Google Scholar
Mighiu PI, Filippi BM, Lam TK. Linking inflammation to the brain-liver axis. Diabetes. 2012;61(6):1350–2.
CAS
PubMed
PubMed Central
Google Scholar
Hotamisligil GS, et al. Reduced tyrosine kinase activity of the insulin receptor in obesity-diabetes. Central role of tumor necrosis factor-alpha. J Clin Invest. 1994;94(4):1543–9.
CAS
PubMed
PubMed Central
Google Scholar
Law IK, et al. Lipocalin-2 deficiency attenuates insulin resistance associated with aging and obesity. Diabetes. 2010;59(4):872–82.
CAS
PubMed
PubMed Central
Google Scholar
Wang Y, et al. Lipocalin-2 is an inflammatory marker closely associated with obesity, insulin resistance, and hyperglycemia in humans. Clin Chem. 2007;53(1):34–41.
CAS
PubMed
Google Scholar
Jha MK, et al. Diverse functional roles of lipocalin-2 in the central nervous system. Neurosci Biobehav Rev. 2015;49:135–56.
CAS
PubMed
Google Scholar
Stavropoulos-Kalinoglou A, et al. Anti-tumour necrosis factor alpha therapy improves insulin sensitivity in normal-weight but not in obese patients with rheumatoid arthritis. Arthritis Res Ther. 2012;14(4):R160.
CAS
PubMed
PubMed Central
Google Scholar
Gonzalez-Gay MA, et al. Insulin resistance in rheumatoid arthritis: the impact of the anti-TNF-alpha therapy. Ann N Y Acad Sci. 2010;1193:153–9.
CAS
PubMed
Google Scholar
MacPherson KP, et al. Peripheral administration of the soluble TNF inhibitor XPro1595 modifies brain immune cell profiles, decreases beta-amyloid plaque load, and rescues impaired long-term potentiation in 5xFAD mice. Neurobiol Dis. 2017;102:81–95.
CAS
PubMed
PubMed Central
Google Scholar
Steed PM, et al. Inactivation of TNF signaling by rationally designed dominant-negative TNF variants. Science. 2003;301(5641):1895–8.
CAS
PubMed
Google Scholar
Dong Y, et al. Essential protective role of tumor necrosis factor receptor 2 in neurodegeneration. Proc Natl Acad Sci U S A. 2016;113(43):12304–9.
CAS
PubMed
PubMed Central
Google Scholar
Ahlemeyer B, et al. Endogenous murine amyloid-beta peptide assembles into aggregates in the aged C57BL/6J mouse suggesting these animals as a model to study pathogenesis of amyloid-beta plaque formation. J Alzheimers Dis. 2018;61(4):1425–50.
CAS
PubMed
Google Scholar
Ungaro F, et al. Actors and factors in the resolution of intestinal inflammation: lipid mediators as a new approach to therapy in inflammatory bowel diseases. Front Immunol. 2017;8:1331.
PubMed
PubMed Central
Google Scholar
Want EJ, et al. Global metabolic profiling of animal and human tissues via UPLC-MS. Nat Protoc. 2013;8(1):17–32.
CAS
PubMed
Google Scholar
de Sousa Rodrigues ME, et al. Chronic psychological stress and high-fat high-fructose diet disrupt metabolic and inflammatory gene networks in the brain, liver, and gut and promote behavioral deficits in mice. Brain Behav Immun. 2017;59:158–72.
PubMed
Google Scholar
Fu Z, et al. Long-term high-fat diet induces hippocampal microvascular insulin resistance and cognitive dysfunction. Am J Physiol Endocrinol Metab. 2017;312(2):E89–e97.
PubMed
Google Scholar
Britton DR, Britton KT. A sensitive open field measure of anxiolytic drug activity. Pharmacol Biochem Behav. 1981;15(4):577–82.
CAS
PubMed
Google Scholar
Samuel VT, Shulman GI. Mechanisms for insulin resistance: common threads and missing links. Cell. 2012;148(5):852–71.
CAS
PubMed
PubMed Central
Google Scholar
R Core Team (2018). R: a language and environment for statistical computing. R Foundation for statistical computing, Vienna, Austria. Available online at https://www.R-project.org/. Accessed 5 Apr 2018.
Smyth GK. Limma: linear models for microarray data. In: Gentleman R, Carey V, Dudoit S, Irizarry R, Huber W, editors. Bioinformatics and computational biology solutions using R and Bioconductor. New York: Springer; 2005. p. 397–420.
Google Scholar
Uppal, K. xMSPANDA. (2019). GitHub Repository, https://github.com/kuppal2/xmsPANDA. Accessed 5 Apr 2018.
Komosinska-Vassev K, Olczyk P, Kuźnik-Trocha K, Jura-Półtorak A, Derkacz A, Purchałka M, Telega A, Olczyk K. Circulating C1q/TNF-Related Protein 3, Omentin-1 and NGAL in Obese Patients with Type 2 Diabetes During Insulin Therapy. J Clin Med. 2019;8(6):805.
PubMed Central
Google Scholar
Chitnis T, Weiner HL. CNS inflammation and neurodegeneration. J Clin Invest. 2017;127(10):3577–87.
PubMed
PubMed Central
Google Scholar
Pedroso JA, et al. Inactivation of SOCS3 in leptin receptor-expressing cells protects mice from diet-induced insulin resistance but does not prevent obesity. Mol Metab. 2014;3(6):608–18.
CAS
PubMed
PubMed Central
Google Scholar
Cao L, Wang Z, Wan W. Suppressor of cytokine signaling 3: emerging role linking central insulin resistance and Alzheimer’s disease. Front Neurosci. 2018;12:417.
PubMed
PubMed Central
Google Scholar
Talbot K, et al. Demonstrated brain insulin resistance in Alzheimer’s disease patients is associated with IGF-1 resistance, IRS-1 dysregulation, and cognitive decline. J Clin Invest. 2012;122(4):1316–38.
CAS
PubMed
PubMed Central
Google Scholar
Moloney AM, et al. Defects in IGF-1 receptor, insulin receptor and IRS-1/2 in Alzheimer’s disease indicate possible resistance to IGF-1 and insulin signalling. Neurobiol Aging. 2010;31(2):224–43.
CAS
PubMed
Google Scholar
Kaidanovich-Beilin O, Lipina T, Vukobradovic I, Roder J, Woodgett JR. Assessment of social interaction behaviors. J Vis Exp. 2011;(48):2473. https://doi.org/10.3791/2473.
Feinstein R, et al. Tumor necrosis factor-alpha suppresses insulin-induced tyrosine phosphorylation of insulin receptor and its substrates. J Biol Chem. 1993;268(35):26055–8.
CAS
PubMed
Google Scholar
Costa L, et al. Impact of 24-month treatment with etanercept, adalimumab, or methotrexate on metabolic syndrome components in a cohort of 210 psoriatic arthritis patients. Clin Rheumatol. 2014;33(6):833–9.
PubMed
Google Scholar
Dominguez H, et al. Metabolic and vascular effects of tumor necrosis factor-alpha blockade with etanercept in obese patients with type 2 diabetes. J Vasc Res. 2005;42(6):517–25.
CAS
PubMed
Google Scholar
Eilenberg W, et al. Neutrophil gelatinase associated lipocalin (NGAL) is elevated in type 2 diabetics with carotid artery stenosis and reduced under metformin treatment. Cardiovasc Diabetol. 2017;16(1):98.
CAS
PubMed
PubMed Central
Google Scholar
Auguet T, et al. Liver lipocalin 2 expression in severely obese women with non alcoholic fatty liver disease. Exp Clin Endocrinol Diabetes. 2013;121(2):119–24.
CAS
PubMed
Google Scholar
Moschen AR, et al. Lipocalin-2: a master mediator of intestinal and metabolic inflammation. Trends Endocrinol Metab. 2017;28(5):388–97.
CAS
PubMed
Google Scholar
Stallhofer J, et al. Lipocalin-2 is a disease activity marker in inflammatory bowel disease regulated by IL-17A, IL-22, and TNF-alpha and modulated by IL23R genotype status. Inflamm Bowel Dis. 2015;21(10):2327–40.
PubMed
Google Scholar
Bolignano D, et al. Neutrophil gelatinase-associated lipocalin levels in patients with crohn disease undergoing treatment with infliximab. J Investig Med. 2010;58(3):569–71.
CAS
PubMed
Google Scholar
Karlsen JR, Borregaard N, Cowland JB. Induction of neutrophil gelatinase-associated lipocalin expression by co-stimulation with interleukin-17 and tumor necrosis factor-alpha is controlled by IkappaB-zeta but neither by C/EBP-beta nor C/EBP-delta. J Biol Chem. 2010;285(19):14088–100.
CAS
PubMed
PubMed Central
Google Scholar
Negrin KA, et al. IL-1 signaling in obesity-induced hepatic lipogenesis and steatosis. PLoS One. 2014;9(9):e107265.
PubMed
PubMed Central
Google Scholar
Houser MC, Tansey MG. The gut-brain axis: is intestinal inflammation a silent driver of Parkinson’s disease pathogenesis? NPJ Parkinsons Dis. 2017;3:3.
PubMed
PubMed Central
Google Scholar
Luck H, et al. Regulation of obesity-related insulin resistance with gut anti-inflammatory agents. Cell Metab. 2015;21(4):527–42.
CAS
PubMed
Google Scholar
Choi J, Lee HW, Suk K. Increased plasma levels of lipocalin 2 in mild cognitive impairment. J Neurol Sci. 2011;305(1–2):28–33.
CAS
PubMed
Google Scholar
Mesquita SD, et al. Lipocalin 2 modulates the cellular response to amyloid beta. Cell Death Differ. 2014;21(10):1588–99.
CAS
PubMed
PubMed Central
Google Scholar
Naude PJ, et al. Lipocalin 2: novel component of proinflammatory signaling in Alzheimer’s disease. FASEB J. 2012;26(7):2811–23.
CAS
PubMed
PubMed Central
Google Scholar
Ferreira AC, et al. Lipocalin-2 is involved in emotional behaviors and cognitive function. Front Cell Neurosci. 2013;7:122.
PubMed
PubMed Central
Google Scholar
Santiago JA, Potashkin JA. Shared dysregulated pathways lead to Parkinson’s disease and diabetes. Trends Mol Med. 2013;19(3):176–86.
CAS
PubMed
Google Scholar
Biessels GJ, Despa F. Cognitive decline and dementia in diabetes mellitus: mechanisms and clinical implications. Nat Rev Endocrinol. 2018;14(10):591–604.
PubMed
PubMed Central
Google Scholar
Kaddurah-Daouk R, et al. Metabolomic changes in autopsy-confirmed Alzheimer’s disease. Alzheimers Dement. 2011;7(3):309–17.
PubMed
Google Scholar
Kaddurah-Daouk R, et al. Alterations in metabolic pathways and networks in Alzheimer’s disease. Transl Psychiatry. 2013;3(4):e244.
CAS
PubMed
PubMed Central
Google Scholar
Giesbertz P, Daniel H. Branched-chain amino acids as biomarkers in diabetes. Curr Opin Clin Nutr Metab Care. 2016;19(1):48–54.
CAS
PubMed
Google Scholar
Hiebert LM. Proteoglycans and diabetes. Curr Pharm Des. 2017;23(10):1500–9.
CAS
PubMed
Google Scholar
Rieder R, Wisniewsk PJ, Alderman BL, Campbel SC. Microbes and mental health: A review. Brain Behav Immun. 2017;66:9-17.
CAS
PubMed
Google Scholar
Noble EE, Hsu TM, Kanoski SE. Gut to brain dysbiosis: mechanisms linking Western diet consumption, the microbiome, and cognitive impairment. Front Behav Neurosci. 2017;11:9.
PubMed
PubMed Central
Google Scholar
van Dijk G, et al. Integrative neurobiology of metabolic diseases, neuroinflammation, and neurodegeneration. Front Neurosci. 2015;9:173.
PubMed
PubMed Central
Google Scholar
Woods LT, et al. Purinergic receptors as potential therapeutic targets in Alzheimer’s disease. Neuropharmacology. 2016;104:169–79.
CAS
PubMed
Google Scholar
Ipata PL, et al. Metabolic network of nucleosides in the brain. Curr Top Med Chem. 2011;11(8):909–22.
CAS
PubMed
Google Scholar
Russo R, et al. Gut-brain axis: role of lipids in the regulation of inflammation, pain and CNS diseases. Curr Med Chem. 2018;25(32):3930–52.
CAS
PubMed
Google Scholar
Heianza Y, et al. Gut microbiota metabolites, amino acid metabolites and improvements in insulin sensitivity and glucose metabolism: the POUNDS Lost trial. Gut. 2019;68(2):263–70.
CAS
PubMed
Google Scholar
Morland C, et al. Propionate enters GABAergic neurons, inhibits GABA transaminase, causes GABA accumulation and lethargy in a model of propionic acidemia. Biochem J. 2018;475(4):749–58.
CAS
PubMed
Google Scholar
Zhang X, Wang B, Li JP. Implications of heparan sulfate and heparanase in neuroinflammation. Matrix Biol. 2014;35:174–81.
PubMed
Google Scholar
Jendresen CB, et al. Overexpression of heparanase lowers the amyloid burden in amyloid-beta precursor protein transgenic mice. J Biol Chem. 2015;290(8):5053–64.
CAS
PubMed
Google Scholar
Zhang Q, et al. Protective effects of low molecular weight chondroitin sulfate on amyloid beta (Abeta)-induced damage in vitro and in vivo. Neuroscience. 2015;305:169–82.
CAS
PubMed
Google Scholar
Iannuzzi C, Borriello M, D'Agostino A, Cimini D, Schiraldi C, Sirangelo I. Protective effect of extractive and biotechnological chondroitin in insulin amyloid and advanced glycation end product- induced toxicity. J Cell Physiol. 2019;234(4):3814-3828.
PubMed
Google Scholar
Abudukadier A, et al. Tetrahydrobiopterin has a glucose-lowering effect by suppressing hepatic gluconeogenesis in an endothelial nitric oxide synthase-dependent manner in diabetic mice. Diabetes. 2013;62(9):3033–43.
CAS
PubMed
PubMed Central
Google Scholar
Kim DG, et al. Non-alcoholic fatty liver disease induces signs of Alzheimer’s disease (AD) in wild-type mice and accelerates pathological signs of AD in an AD model. J Neuroinflammation. 2016;13:1.
PubMed
PubMed Central
Google Scholar