# Modulation and Reprogramming of Adipose Tissue Macrophages in Obesity **Authors:** Yan Liu, Xiaoying Huang, Linfeng Sang, Yang Zhang, Jiajie Cao, Qin Kong PMC · DOI: 10.3390/biom16020339 · Biomolecules · 2026-02-23 ## TL;DR This paper reviews how obesity affects immune cells in fat tissue, leading to inflammation and metabolic issues. ## Contribution The paper provides a comprehensive overview of the metabolic reprogramming and regulatory mechanisms of adipose tissue macrophages in obesity. ## Key findings - Adipose tissue macrophages show metabolic heterogeneity linked to obesity-related inflammation. - Transcriptional and epigenetic mechanisms underlie ATM remodeling in obesity. - Glucose and lipid homeostasis are key pathways affected in ATMs during obesity. ## Abstract Chronic inflammation associated with obesity drives metabolic dysfunctions and induces immune cell maintenance. Adipose tissue macrophages (ATMs), the predominant immune population within adipose depots, exhibit substantial heterogeneity and serve as central pathological mediators in obesity-induced adipose inflammation and metabolic dysregulation. In this review, we highlight the reprogramming of ATMs’ metabolic pathways, including glucose and lipid homeostasis associated with obesity, with a focus on chronic metabolic inflammation. Additionally, we discuss underlying mechanisms supporting ATMs remodeling in obesity, including transcriptional control and epigenetic regulation. ## Linked entities - **Diseases:** obesity (MONDO:0011122) ## Full-text entities - **Genes:** Gpr155 (G protein-coupled receptor 155) [NCBI Gene 68526] {aka 1110017O10Rik, DEPDC3, F730029F15Rik, LYCHOS, PGR22}, Slc16a14 (solute carrier family 16 (monocarboxylic acid transporters), member 14) [NCBI Gene 71781] {aka 1110004H10Rik}, Pdia3 (protein disulfide isomerase associated 3) [NCBI Gene 14827] {aka 58kDa, ERp57, ERp60, ERp61, Erp, Grp58}, Ppargc1a (peroxisome proliferative activated receptor, gamma, coactivator 1 alpha) [NCBI Gene 19017] {aka A830037N07Rik, Gm11133, PGC-1, PPARGC-1-alpha, Pgc-1alpha, Pgc1}, Maoa (monoamine oxidase A) [NCBI Gene 17161] {aka 1110061B18Rik}, Scarb1 (scavenger receptor class B, member 1) [NCBI Gene 20778] {aka CD36, Cd36l1, Chohd1, Cla-1, Cla1, D5Ertd460e}, Irf4 (interferon regulatory factor 4) [NCBI Gene 16364] {aka IRF-4, LSIRF, NF-EM5, Spip}, COX2 (cytochrome c oxidase subunit II) [NCBI Gene 17709], Ifnb1 (interferon beta 1, fibroblast) [NCBI Gene 15977] {aka IFN-beta, IFNB, If1da1, Ifb}, Epas1 (endothelial PAS domain protein 1) [NCBI Gene 13819] {aka HIF-2alpha, HIF2A, HLF, HRF, MOP2, bHLHe73}, Crebzf (CREB/ATF bZIP transcription factor) [NCBI Gene 233490] {aka 1110034C16Rik, 6330417B10Rik, LAZip, LAZipII, SMILE, Zf}, Retnla (resistin like alpha) [NCBI Gene 57262] {aka 1810019L16Rik, Fizz-1, Fizz1, HIMF, RELM-alpha, RELMa}, Idh1 (isocitrate dehydrogenase 1 (NADP+), soluble) [NCBI Gene 15926] {aka E030024J03Rik, Id-1, Idh-1, Idpc}, Ghitm (growth hormone inducible transmembrane protein) [NCBI Gene 66092] {aka 1010001P14Rik, MICS1, PTD010, Tmbim5}, Egln1 (egl-9 family hypoxia-inducible factor 1) [NCBI Gene 112405] {aka C1orf12, HIF-PH2, HPH-2, Hif-p4h-2, ORF13, Phd2}, Klf2 (Kruppel-like transcription factor 2 (lung)) [NCBI Gene 16598] {aka Lklf}, Xbp1 (X-box binding protein 1) [NCBI Gene 22433] {aka D11Ertd39e, TREB-5, TREB5, XBP-1}, Il6 (interleukin 6) [NCBI Gene 16193] {aka Il-6}, Trp53-ps (transformation related protein 53, pseudogene) [NCBI Gene 22060], Syk (spleen tyrosine kinase) [NCBI Gene 20963] {aka Sykb}, Il18 (interleukin 18) [NCBI Gene 16173] {aka Igif, Il-18}, Itga9 (integrin alpha 9) [NCBI Gene 104099] {aka (alpha)9, 2610002H11Rik, 6720458D17Rik, D130073C02, D9Ertd428e}, 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}, Nfe2l2 (nuclear factor, erythroid derived 2, like 2) [NCBI Gene 18024] {aka Nrf2}, Stat6 (signal transducer and activator of transcription 6) [NCBI Gene 20852], Ern1 (endoplasmic reticulum to nucleus signalling 1) [NCBI Gene 78943] {aka 9030414B18Rik, Ire1a, Ire1alpha, Ire1p}, Abca1 (ATP-binding cassette, sub-family A member 1) [NCBI Gene 11303] {aka ABC-1, Abc1}, Lamp2 (lysosomal-associated membrane protein 2) [NCBI Gene 16784] {aka CD107b, LGP-B, Lamp II, Lamp-2, Lamp-2a, Lamp-2b}, Rara (retinoic acid receptor, alpha) [NCBI Gene 19401] {aka Nr1b1, RAR, RARalpha1}, Ep300 (E1A binding protein p300) [NCBI Gene 328572] {aka A430090G16, A730011L11, KAT3B, p300, p300 HAT}, Lyve1 (lymphatic vessel endothelial hyaluronan receptor 1) [NCBI Gene 114332] {aka 1200012G08Rik, Crsbp-1, Lyve-1, Xlkd1}, Il1a (interleukin 1 alpha) [NCBI Gene 16175] {aka Il-1a}, Il1b (interleukin 1 beta) [NCBI Gene 16176] {aka IL-1beta, Il-1b}, Pparg (peroxisome proliferator activated receptor gamma) [NCBI Gene 19016] {aka Nr1c3, PPAR-gamma, PPAR-gamma2, PPARgamma, PPARgamma2}, Cybb (cytochrome b-245, beta polypeptide) [NCBI Gene 13058] {aka CGD91-phox, Cgd, Cyd, Nox2, gp91-1, gp91phox}, Ern2 (endoplasmic reticulum to nucleus signalling 2) [NCBI Gene 26918] {aka Ern1, Ire1, Ire1b, ire1-beta, mIre1}, Nox4 (NADPH oxidase 4) [NCBI Gene 50490], Ccl2 (C-C motif chemokine ligand 2) [NCBI Gene 20296] {aka HC11, JE, MCAF, MCP-1, MCP1, SMC-CF}, Cd63 (CD63 antigen) [NCBI Gene 12512] {aka ME491, Tspan30}, Nqo1 (NAD(P)H dehydrogenase, quinone 1) [NCBI Gene 18104] {aka Dia4, Dtd, Nmo-1, Nmo1, Nmor1, Ox-1}, G6pd2 (glucose-6-phosphate dehydrogenase 2) [NCBI Gene 14380] {aka G6pdx-ps1, Gpd-2, Gpd2}, Rps6kb1 (ribosomal protein S6 kinase B1) [NCBI Gene 72508] {aka 2610318I15Rik, P70S6K1, S6K, S6K-beta-1, S6K1, p70 S6K-alpha}, Atf3 (activating transcription factor 3) [NCBI Gene 11910] {aka LRG-21}, Itgax (integrin alpha X) [NCBI Gene 16411] {aka Cd11c, Cr4, N418}, Tbk1 (TANK-binding kinase 1) [NCBI Gene 56480] {aka 1200008B05Rik}, Keap1 (kelch-like ECH-associated protein 1) [NCBI Gene 50868] {aka INRF2, mKIAA0132}, Tlr4 (toll-like receptor 4) [NCBI Gene 21898] {aka Lps, Ly87, Ran/M1, Rasl2-8}, Adrb2 (adrenergic receptor, beta 2) [NCBI Gene 11555] {aka Adrb-2, Badm, Gpcr7}, Atm (ataxia telangiectasia mutated) [NCBI Gene 11920] {aka C030026E19Rik}, Hmox1 (heme oxygenase 1) [NCBI Gene 15368] {aka D8Wsu38e, HO-1, HO1, Hemox, Hmox, Hsp32}, Cd209b (CD209b antigen) [NCBI Gene 69165] {aka 1810030I22Rik, Clec4m, DC-SIGNR1, OtB7, SIGNR1, mSIGNR1}, Chrna2 (cholinergic receptor nicotinic alpha 2 subunit) [NCBI Gene 110902] {aka Acra-2, Acra2}, T(10;11)Rl (reciprocal translocation, Chr 10 and 11, Russell) [NCBI Gene 21033] {aka TRl}, Ctss (cathepsin S) [NCBI Gene 13040] {aka Cats}, Ms4a3 (membrane-spanning 4-domains, subfamily A, member 3) [NCBI Gene 170813] {aka HTm4}, Eif2ak4 (eukaryotic translation initiation factor 2 alpha kinase 4) [NCBI Gene 27103] {aka 2610011M03, GCN2, MGCN2}, Ube2m (ubiquitin-conjugating enzyme E2M) [NCBI Gene 22192] {aka 2510040H03Rik, UBC12, Ubc-rs2}, Lpl (lipoprotein lipase) [NCBI Gene 16956], Creb1 (cAMP responsive element binding protein 1) [NCBI Gene 12912] {aka 2310001E10Rik, 3526402H21Rik, Creb, Creb-1}, Akt1 (Akt serine/threonine kinase 1) [NCBI Gene 11651] {aka Akt, LTR-akt, PKB, PKB/Akt, PKBalpha, Rac} - **Diseases:** Obesity (MESH:D009765), hypoxic (MESH:D002534), MAFLD (MESH:D005234), CLS (MESH:D038921), metabolic dysregulation (MESH:D021081), Metabolic Dysfunction (MESH:D008659), Hypoxia (MESH:D000860), hyperlipidemia (MESH:D006949), fibrosis (MESH:D005355), IR (MESH:C537629), hyperglycemia (MESH:D006943), injury to (MESH:D014947), Inflammatory (MESH:D007249), mitochondrial FAO (MESH:D028361), diabetes (MESH:D003920), lactic acidosis (MESH:D000140), cancer (MESH:D009369), NAFLD (MESH:D065626), ESCC (MESH:D000077277), CKD (MESH:D051436), overnutrition (MESH:D044343), arterial inflammation (MESH:D001167), hypercholesterolemia (MESH:D006937), Adipose tissue (MESH:D018205), T2D (MESH:D003924), CLSs (MESH:D000072717), hyperplasia (MESH:D006965), diabetic nephropathy (MESH:D003928), immune dysregulation (OMIM:614878), glucose intolerance (MESH:D018149), sepsis (MESH:D018805), chronic (MESH:D002908), atherogenesis (MESH:D050197), hyperinsulinemia (MESH:D006946), hypertrophy (MESH:D006984), infections (MESH:D007239), cardiovascular disease (MESH:D002318), vascular restenosis (MESH:D006083), Insulin Resistance (MESH:D007333), toxicity (MESH:D064420) - **Chemicals:** Omega-6 fatty acids (MESH:D043371), Nigericin (MESH:D009550), leucine (MESH:D007930), lactoyl-CoA (MESH:C047009), phospholipid (MESH:D010743), EPA (MESH:D015118), acetylcholine (MESH:D000109), malonyl-CoA (MESH:D008316), PGE2 (MESH:D015232), FFA (MESH:D005230), acetyl CoA (MESH:D000105), AA (MESH:D016718), iron (MESH:D007501), BCAA (MESH:D000597), Rhein (MESH:C020491), Sarcosine (MESH:D012521), ketone body (MESH:D007657), artesunate (MESH:D000077332), Cholesterol (MESH:D002784), LA (MESH:D019787), beta-HB (MESH:D020155), Itaconic acid (MESH:C005229), pyruvate (MESH:D019289), fat (MESH:D005223), EGCG (MESH:C045651), Succinate (MESH:D019802), Oxygen (MESH:D010100), prostaglandins (MESH:D011453), isoleucine (MESH:D007532), L-lactate (MESH:D019344), Omega-3 fatty acids (MESH:D015525), isocitrate (MESH:C034219), TCA (MESH:D014233), LXA4 (MESH:C040527), Etomoxir (MESH:C054207), pentose phosphate (MESH:D010428), TG (MESH:D014280), ketone (MESH:D007659), citrate (MESH:D019343), ATP (MESH:D000255), 25-HC (MESH:C007997), DHA (MESH:D004281), palmitic acid (MESH:D019308), LPS (MESH:D008070), cysteine (MESH:D003545), Lipid (MESH:D008055), MLN4924 (MESH:C539933), NAD (MESH:D009243), CA (MESH:D002118), Glucose (MESH:D005947), palmitate (MESH:D010168), dextran (MESH:D003911), superoxide (MESH:D013481), DNL (-), 2-BP (MESH:C022776), NADPH (MESH:D009249), amino acid (MESH:D000596), phosphatidylcholine (MESH:D010713), GLA (MESH:D017965), fatty acid (MESH:D005227) - **Species:** Mus musculus (house mouse, species) [taxon 10090], Rheum rhabarbarum (garden rhubarb, species) [taxon 3621], Homo sapiens (human, species) [taxon 9606] - **Mutations:** cysteine residue at position 126 - **Cell lines:** RAW264.6 — Mus musculus (Mouse), Mouse leukemia, Cancer cell line (CVCL_0493), THP-1 — Homo sapiens (Human), Childhood acute monocytic leukemia, Cancer cell line (CVCL_0006) ## Full text _Full body text omitted from this summary view._ Fetch the complete paper as Markdown: https://tomesphere.com/paper/PMC12937715/full.md ## Figures 15 figures with captions in the complete paper: https://tomesphere.com/paper/PMC12937715/full.md ## References 211 references — full list in the complete paper: https://tomesphere.com/paper/PMC12937715/full.md --- Source: https://tomesphere.com/paper/PMC12937715