# Obesity-Induced Brain Neuroinflammatory and Mitochondrial Changes **Authors:** Luisa O. Schmitt, Joana M. Gaspar PMC · DOI: 10.3390/metabo13010086 · 2023-01-05 ## TL;DR This review explains how obesity causes brain inflammation and mitochondrial issues, which may lead to cognitive decline and neurodegenerative problems. ## Contribution The paper reviews how obesity and high-fat diets affect brain neuroinflammation and mitochondrial function, linking metabolic issues to cognitive decline. ## Key findings - Obesity causes chronic low-grade inflammation in adipose tissue, which may contribute to brain disorders. - Mitochondrial dysfunction in the brain is linked to obesity-related inflammation and oxidative stress. - Neuronal damage and cognitive decline may result from impaired mitochondrial activity due to obesity. ## Abstract Obesity is defined as abnormal and excessive fat accumulation, and it is a risk factor for developing metabolic and neurodegenerative diseases and cognitive deficits. Obesity is caused by an imbalance in energy homeostasis resulting from increased caloric intake associated with a sedentary lifestyle. However, the entire physiopathology linking obesity with neurodegeneration and cognitive decline has not yet been elucidated. During the progression of obesity, adipose tissue undergoes immune, metabolic, and functional changes that induce chronic low-grade inflammation. It has been proposed that inflammatory processes may participate in both the peripheral disorders and brain disorders associated with obesity, including the development of cognitive deficits. In addition, mitochondrial dysfunction is related to inflammation and oxidative stress, causing cellular oxidative damage. Preclinical and clinical studies of obesity and metabolic disorders have demonstrated mitochondrial brain dysfunction. Since neuronal cells have a high energy demand and mitochondria play an important role in maintaining a constant energy supply, impairments in mitochondrial activity lead to neuronal damage and dysfunction and, consequently, to neurotoxicity. In this review, we highlight the effect of obesity and high-fat diet consumption on brain neuroinflammation and mitochondrial changes as a link between metabolic dysfunction and cognitive decline. ## Linked entities - **Diseases:** obesity (MONDO:0011122) ## Full-text entities - **Genes:** Nlrp3 (NLR family, pyrin domain containing 3) [NCBI Gene 216799] {aka AGTAVPRL, AII/AVP, Cias1, FCAS, FCU, MWS}, Sirt1 (sirtuin 1) [NCBI Gene 309757] {aka Sir2}, Socs3 (suppressor of cytokine signaling 3) [NCBI Gene 12702] {aka Cis3, Cish3, EF-10, Ef10, SSI-3, Ssi3}, Tlr4 (toll-like receptor 4) [NCBI Gene 29260], H2 (histocompatibility-2, MHC) [NCBI Gene 111364] {aka H-2, MHC-II}, Nup62 (nucleoporin 62) [NCBI Gene 18226] {aka D7Ertd649e, Nupc1, p62}, Tnf (tumor necrosis factor) [NCBI Gene 24835] {aka RATTNF, TNF-alpha, Tnfa}, Il1b (interleukin 1 beta) [NCBI Gene 24494] {aka IL-1F2}, Pomc (pro-opiomelanocortin-alpha) [NCBI Gene 18976] {aka ACTH, BE, Beta-LPH, Clip, Gamma-LPH, Npp}, Fis1 (fission, mitochondrial 1) [NCBI Gene 66437] {aka 2010003O14Rik, Ttc11}, Nfkb1 (nuclear factor of kappa light polypeptide gene enhancer in B cells 1, p105) [NCBI Gene 18033] {aka NF-KB1, NF-kappaB, NF-kappaB1, p105, p50, p50/p105}, Glrx (glutaredoxin) [NCBI Gene 93692] {aka D13Wsu156e, Glrx1, Grx1, TTase}, Tlr4 (toll-like receptor 4) [NCBI Gene 21898] {aka Lps, Ly87, Ran/M1, Rasl2-8}, Pink1 (PTEN induced putative kinase 1) [NCBI Gene 68943] {aka 1190006F07Rik, BRPK, mFLJ00387}, Ptgs2 (prostaglandin-endoperoxide synthase 2) [NCBI Gene 29527] {aka COX-2, Cox2, PGHS-2, PHS II, Pghs2}, Il1b (interleukin 1 beta) [NCBI Gene 16176] {aka IL-1beta, Il-1b}, Il6 (interleukin 6) [NCBI Gene 16193] {aka Il-6}, Tnf (tumor necrosis factor) [NCBI Gene 21926] {aka DIF, TNF-a, TNF-alpha, TNFSF2, TNFalpha, Tnfa}, Dnm1l (dynamin 1-like) [NCBI Gene 74006] {aka 6330417M19Rik, Dlp1, Dnmlp1, Drp1, python}, Nfkbia (nuclear factor of kappa light polypeptide gene enhancer in B cells inhibitor, alpha) [NCBI Gene 18035] {aka Nfkbi}, Lep (leptin) [NCBI Gene 16846] {aka ob, obese}, Ikbkb (inhibitor of kappaB kinase beta) [NCBI Gene 16150] {aka IKK-2, IKK-B, IKK-beta, IKK2, IKK[b], IKKbeta}, Ndufs4 (NADH:ubiquinone oxidoreductase core subunit S4) [NCBI Gene 17993] {aka 6720411N02Rik, C1-18k}, Agrp (agouti related neuropeptide) [NCBI Gene 11604] {aka Agrt, Art}, Gfap (glial fibrillary acidic protein) [NCBI Gene 14580], Ndufs5 (NADH:ubiquinone oxidoreductase core subunit S5) [NCBI Gene 595136], Mfn2 (mitofusin 2) [NCBI Gene 170731] {aka D630023P19Rik, Fzo}, Lepr (leptin receptor) [NCBI Gene 16847] {aka B219, LEP-R, LEPROT, Leprb, Modb1, OB-RGRP}, Sirt3 (sirtuin 3) [NCBI Gene 64384] {aka 2310003L23Rik, Sir2l3}, Glrx2 (glutaredoxin 2) [NCBI Gene 69367] {aka 1700010P22Rik, Grx2}, Dpp4 (dipeptidylpeptidase 4) [NCBI Gene 25253] {aka CD26, DPPIV}, Il6 (interleukin 6) [NCBI Gene 24498] {aka ILg6, Ifnb2}, Iba1 (induction of brown adipocytes 1) [NCBI Gene 114737], Map3k7 (mitogen-activated protein kinase kinase kinase 7) [NCBI Gene 26409] {aka B430101B05, Tak1}, Jun (Jun proto-oncogene, AP-1 transcription factor subunit) [NCBI Gene 16476] {aka AP-1, Junc, c-jun}, Mff (mitochondrial fission factor) [NCBI Gene 75734] {aka 5230400G24Rik}, Cat (catalase) [NCBI Gene 24248] {aka CS1, Cas1, Cat01, Catl, Cs-1}, Opa1 (OPA1, mitochondrial dynamin like GTPase) [NCBI Gene 74143] {aka 1200011N24Rik, lilr3, mKIAA0567}, Mfn1 (mitofusin 1) [NCBI Gene 67414] {aka 2310002F04Rik, 6330416C07Rik, D3Ertd265e, HR2, mKIAA4032}, Ppargc1a (PPARG coactivator 1 alpha) [NCBI Gene 83516] {aka LRPGC1, PGC-1v, PGCvf, PGCvf-1, PGCvf1, Ppargc1} - **Diseases:** Hypothalamic Neuroinflammation (MESH:D007027), injury to people or property (MESH:C000719191), dementia (MESH:D003704), brain diseases (MESH:D001927), metabolic dysmetabolism (MESH:D024821), hippocampal alterations (MESH:D000092223), metabolic and neurodegenerative diseases (MESH:D019636), noncommunicable diseases (MESH:D000073296), astrogliosis (MESH:D005911), chronic inflammation (MESH:D007249), disorders (MESH:D009358), Obese (MESH:D009765), vascular dementia (MESH:D015140), Insulin resistance (MESH:D007333), type 2 diabetes (MESH:D003924), cerebral energy gain (MESH:D015430), neuronal apoptosis (MESH:D065703), brain atrophy (MESH:C566985), adiposity (MESH:D018205), cognitive failure (MESH:D051437), endothelial dysfunction (MESH:D014652), deficits in learning and memory (MESH:D007859), neuronal damage (MESH:D009410), 3xTg-AD (MESH:D000544), metabolic and neurological conditions (MESH:D001928), memory dysfunction (MESH:D008569), Diabetes (MESH:D003920), Weight loss (MESH:D015431), synaptic dysfunction (MESH:C536122), musculoskeletal disease (MESH:D009140), Brain Neuroinflammatory (MESH:D000090862), metabolic and cardiovascular diseases (MESH:D002318), premature death (MESH:D003643), Dysfunctional mitochondria (MESH:C564971), cognitive alterations (MESH:D003072), metabolic disease (MESH:D008659), cerebral hypersensitivity (MESH:D004342), brain injury (MESH:D001930), cancer (MESH:D009369), neurotoxicity (MESH:D020258), neuronal dysfunction (MESH:D009461), function (MESH:D003291), Mitochondrial (MESH:D028361), brain damage (MESH:D001925), overweight (MESH:D050177), type 1 diabetes (MESH:D003922), neuronal damage and dysfunction (MESH:D007674), Depressive (MESH:D003866), executive dysfunction (MESH:D006331) - **Chemicals:** calcium (MESH:D002118), NO (MESH:D009569), glycine (MESH:D005998), GSH (MESH:D005978), tricarboxylic acid (MESH:D014233), I (MESH:D007455), malondialdehyde (MESH:D008315), sucrose (MESH:D013395), ADP (MESH:D000244), thiol (MESH:D013438), lipid (MESH:D008055), blood glucose (MESH:D001786), STZ (MESH:D013311), ROS (MESH:D017382), peroxide (MESH:D010545), DCFHDA (MESH:C029569), Fatty acid (MESH:D005227), O2 (MESH:D010100), palmitic acid (MESH:D019308), glucose (MESH:D005947), vildagliptin (MESH:D000077597), GSSG (MESH:D019803), ubiquinone (MESH:D014451), NADH (MESH:D009243), palmitate (MESH:D010168), FADH2 (MESH:C058805), disulfide (MESH:D004220), acetyl-CoA. (MESH:D000105), ubiquinol (MESH:C003741), Ca2+ (-), ceramide (MESH:D002518), H2O2 (MESH:D006861), fat (MESH:D005223), N-acetylcysteine (MESH:D000111), water (MESH:D014867), monounsaturated fatty acids (MESH:D005229), ATP (MESH:D000255) - **Species:** Mus musculus (house mouse, species) [taxon 10090], Rattus norvegicus (brown rat, species) [taxon 10116], Homo sapiens (human, species) [taxon 9606] ## Figures 2 figures with captions in the complete paper: https://tomesphere.com/paper/PMC9865135/full.md --- Source: https://tomesphere.com/paper/PMC9865135