# Lipid metabolism in homeostasis and disease

**Authors:** Zhenghao Li, Wende Deng, Lanxuan Yang, Changheng Tang, Jian-Min Yue, Olivia Monteiro, Daniel T. Baptista-Hon, Ting Li

PMC · DOI: 10.1038/s41392-025-02357-x · 2026-02-16

## TL;DR

This review explores how lipid metabolism affects immune cells and contributes to diseases like cancer and diabetes, highlighting potential new treatments.

## Contribution

The paper provides a comprehensive overview of lipid metabolism's role in immune cell regulation and its therapeutic implications.

## Key findings

- Lipid metabolism significantly influences immune cell function and disease progression.
- Regulation of lipid metabolism involves multiple levels, including genetic and epigenetic mechanisms.
- Targeting lipid metabolism offers new therapeutic strategies for immune-related diseases.

## Abstract

Lipid metabolism is essential for maintaining cellular homeostasis, and its dysregulation is linked to various diseases, including cancer, cardiovascular disease, and diabetes. Immune cells, such as macrophages, T cells, B cells, and neutrophils, rely on lipid metabolism for their function, which impacts both innate and adaptive immune responses. Understanding how lipid metabolism influences immune cells is crucial, as it can reveal new therapeutic opportunities for immune-mediated diseases. In this review, we provide a retrospective summary of the research history and milestone events in lipid metabolism research and highlight the importance of lipid metabolism in immune cells. In addition to discussing the various lipid functions, transport, and signaling pathways involved in lipid metabolism, we mainly explore the regulation of immune cell behavior by lipid metabolism, focusing on the roles of lipid metabolites in immune cell proliferation, differentiation, and activation. We further highlight multilevel regulatory mechanisms, including genetic, epigenetic, posttranscriptional, and posttranslational regulation, and their impact on immune cell function. Additionally, we discuss the role of lipid metabolism in diseases such as autoimmune diseases, cancer, neurodegenerative diseases, cardiovascular diseases, aging, and metabolic disorders. Finally, we summarize therapeutic strategies targeting lipid metabolism, the progress of global clinical trials, and future research directions, including lipid-derived biomarkers and innovative therapeutic approaches.

## Linked entities

- **Diseases:** cancer (MONDO:0004992), cardiovascular disease (MONDO:0004995), diabetes (MONDO:0005015)

## Full-text entities

- **Genes:** IL13RA1 (interleukin 13 receptor subunit alpha 1) [NCBI Gene 3597] {aka CD213A1, CT19, IL-13Ra, NR4}, IL2 (interleukin 2) [NCBI Gene 3558] {aka IL-2, TCGF, lymphokine}, MIR21 (microRNA 21) [NCBI Gene 406991] {aka MIRN21, hsa-mir-21, miR-21, miRNA21}, Plin2 (perilipin 2) [NCBI Gene 298199] {aka Adfp, Adrp}, Hdac9 (histone deacetylase 9) [NCBI Gene 79221] {aka D030072B18Rik, HD7B, HD9, HDRP, Hdac7b, Mitr}, Srebf1 (sterol regulatory element binding transcription factor 1) [NCBI Gene 20787] {aka ADD1, SREBP1, bHLHd1}, MIR148A (microRNA 148a) [NCBI Gene 406940] {aka MIRN148, MIRN148A, hsa-mir-148, mir-148a}, PTPN2 (protein tyrosine phosphatase non-receptor type 2) [NCBI Gene 5771] {aka PTN2, PTPT, TC-PTP, TC45, TC48, TCELLPTP}, Lcn2 (lipocalin 2) [NCBI Gene 16819] {aka 24p3, NRL, Sip24}, Hmgcr (3-hydroxy-3-methylglutaryl-Coenzyme A reductase) [NCBI Gene 15357] {aka HMG-CoAR, Red}, Trem1 (triggering receptor expressed on myeloid cells 1) [NCBI Gene 58217], XYLT2 (xylosyltransferase 2) [NCBI Gene 64132] {aka PXYLT2, SOS, XT-II, XT2, xylT-II}, PNPLA2 (patatin like domain 2, triacylglycerol lipase) [NCBI Gene 57104] {aka 1110001C14Rik, ATGL, FP17548, PEDF-R, TTS-2.2, TTS2}, BTK (Bruton tyrosine kinase) [NCBI Gene 695] {aka AGMX1, AT, ATK, BPK, IGHD3, IMD1}, EPHX2 (epoxide hydrolase 2) [NCBI Gene 2053] {aka ABHD20, CEH, SEH}, WTAP (WT1 associated protein) [NCBI Gene 9589] {aka Mum2}, Tnfrsf1a (tumor necrosis factor receptor superfamily, member 1a) [NCBI Gene 21937] {aka CD120a, FPF, TNF-R, TNF-R-I, TNF-R1, TNF-R55}, ABCG1 (ATP binding cassette subfamily G member 1) [NCBI Gene 9619] {aka ABC8, WHITE1}, IL7 (interleukin 7) [NCBI Gene 3574] {aka IL-7, IMD130}, Stat3 (signal transducer and activator of transcription 3) [NCBI Gene 20848] {aka 1110034C02Rik, Aprf}, Scap (SREBF chaperone) [NCBI Gene 235623] {aka 9530044G19, mKIAA0199}, PPARG (peroxisome proliferator activated receptor gamma) [NCBI Gene 5468] {aka CIMT1, FPLD3, GLM1, NR1C3, PPARG1, PPARG2}, Mavs (mitochondrial antiviral signaling protein) [NCBI Gene 228607] {aka D430028G21Rik, IPS-1, Visa, cardif}, Ffar3 (free fatty acid receptor 3) [NCBI Gene 233080] {aka Gm478, Gpr41}, SYK (spleen associated tyrosine kinase) [NCBI Gene 6850] {aka IMD82, p72-Syk}, CD4 (CD4 molecule) [NCBI Gene 920] {aka CD4mut, IMD79, Leu-3, OKT4D, T4}, Akt1 (Akt serine/threonine kinase 1) [NCBI Gene 11651] {aka Akt, LTR-akt, PKB, PKB/Akt, PKBalpha, Rac}, ZAP70 (zeta chain of T cell receptor associated protein kinase 70) [NCBI Gene 7535] {aka ADMIO2, IMD48, SRK, STCD, STD, TZK}, SELE (selectin E) [NCBI Gene 6401] {aka CD62E, ELAM, ELAM1, ESEL, LECAM2, selectin-e}, Rad18 (RAD18 E3 ubiquitin protein ligase) [NCBI Gene 58186] {aka 2810024C04Rik, Rad18sc}, Foxp3 (forkhead box P3) [NCBI Gene 20371] {aka JM2, scurfin, sf}, PIK3CD (phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit delta) [NCBI Gene 5293] {aka APDS, IMD14, IMD14A, IMD14B, P110DELTA, PI3K}, S1PR1 (sphingosine-1-phosphate receptor 1) [NCBI Gene 1901] {aka CD363, CHEDG1, D1S3362, ECGF1, EDG-1, EDG1}, CD19 (CD19 molecule) [NCBI Gene 930] {aka B4, CVID3}, PIK3CB (phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit beta) [NCBI Gene 5291] {aka P110BETA, PI3K, PI3KBETA, PIK3C1}, CCR6 (C-C motif chemokine receptor 6) [NCBI Gene 1235] {aka BN-1, C-C CKR-6, CC-CKR-6, CCR-6, CD196, CKR-L3}, SMAD3 (SMAD family member 3) [NCBI Gene 4088] {aka HSPC193, HsT17436, JV15-2, LDS1C, LDS3, MADH3}, S1pr2 (sphingosine-1-phosphate receptor 2) [NCBI Gene 14739] {aka 1100001A16Rik, Edg5, Gpcr13, H218, LPb2, S1P2}, Cd40 (CD40 antigen) [NCBI Gene 21939] {aka Bp50, GP39, HIGM1, IGM, IMD3, T-BAM}, Rela (Rela proto-oncogene, NFKB subunit) [NCBI Gene 19697] {aka p65, p65 NF-kappa B, p65 NFkB}, Ccr7 (C-C motif chemokine receptor 7) [NCBI Gene 12775] {aka CC-CKR-7, CCR-7, CD197, Cdw197, Cmkbr7, EBI1}, Ldlr (low density lipoprotein receptor) [NCBI Gene 16835] {aka Hlb301}, PLIN2 (perilipin 2) [NCBI Gene 123] {aka ADFP, ADRP}, Ephx2 (epoxide hydrolase 2, cytoplasmic) [NCBI Gene 13850] {aka CEH, Eph2, SEH, sEP}, ACACA (acetyl-CoA carboxylase alpha) [NCBI Gene 31] {aka ACAC, ACACAD, ACACalpha, ACC, ACC1, ACCA}, Ch25h (cholesterol 25-hydroxylase) [NCBI Gene 12642] {aka m25OH}, ESR1 (estrogen receptor 1) [NCBI Gene 2099] {aka ER, ESR, ESRA, ESTRR, Era, NR3A1}, Ppara (peroxisome proliferator activated receptor alpha) [NCBI Gene 19013] {aka 4933429D07Rik, Nr1c1, PPAR-alpha, PPARalpha, Ppar}, Mul1 (mitochondrial ubiquitin ligase activator of NFKB 1) [NCBI Gene 68350] {aka 0610009K11Rik, Gide, Tnrip-1}, SCD5 (stearoyl-CoA desaturase 5) [NCBI Gene 79966] {aka ACOD4, DFNA79, FADS4, HSCD5, SCD2, SCD4}, Cd28 (CD28 antigen) [NCBI Gene 12487], TRIB1 (tribbles pseudokinase 1) [NCBI Gene 10221] {aka C8FW, GIG-2, GIG2, SKIP1, TRB-1, TRB1}, Gm12551 (perilipin 2 pseudogene) [NCBI Gene 101055843], Ormdl1 (ORM1-like 1 (S. cerevisiae)) [NCBI Gene 227102] {aka C730042F17Rik}, Cpt1a (carnitine palmitoyltransferase 1a, liver) [NCBI Gene 12894] {aka C730027G07, CPTI, Cpt1}, Pnpla2 (patatin-like phospholipase domain containing 2) [NCBI Gene 66853] {aka 0610039C21Rik, 1110001C14Rik, Atgl, TTS-2.2}, IFNG (interferon gamma) [NCBI Gene 3458] {aka IFG, IFI, IMD69}, APOB (apolipoprotein B) [NCBI Gene 338] {aka FCHL2, FLDB, LDLCQ4, apoB-100, apoB-48}, FCER1A (Fc epsilon receptor Ia) [NCBI Gene 2205] {aka FCE1A, FCERIA, FcERI}, LIPA (lipase A, lysosomal acid type) [NCBI Gene 3988] {aka CESD, LAL}
- **Diseases:** liver damage (MESH:D056486), peripheral neuropathy (MESH:D010523), FAO (MESH:C536560), muscle pain (MESH:D063806), T1DM (MESH:D003922), pulmonary fibrosis (MESH:D011658), dementia (MESH:D003704), amyloid (MESH:C000718787), coronary artery disease (MESH:D003324), ovarian cancer (MESH:D010051), allergic diseases (MESH:D004342), liver injury (MESH:D017093), T2DM (MESH:D003924), fat degeneration (MESH:D009410), proinflammatory cytokines (MESH:D000080424), enteric virus infection (MESH:D004751), bacterial infections (MESH:D001424), organ damage (MESH:D000092124), hypercholesterolemia (MESH:D006937), neuropathic pain (MESH:D009437), heart failure (MESH:D006333), renal lesions (MESH:D007674), IBD (MESH:D015212), EAE (MESH:D004681), breast cancer (MESH:D001943), familial chylomicronemia syndrome (MESH:D008072), cognitive decline (MESH:D003072), ulcerative colitis (MESH:D003093), brain cancer (MESH:D001932), hypertriglyceridemia (MESH:D015228), chronic (MESH:D002908), memory and executive dysfunction (MESH:D008569), infectious disease (MESH:D003141), HIV infection (MESH:D015658), immune dysregulation (OMIM:614878), impaired glucose tolerance (MESH:D018149), bacterial and fungal infections (MESH:D009181), indigestion (MESH:D004415), primary biliary cholangitis (MESH:D008105), hepatocellular carcinoma (MESH:D006528), MS (MESH:D009103), intestinal injury (MESH:D007410), lipid (MESH:D011017), necrosis (MESH:D009336), hypertension (MESH:D006973), abnormalities in lipid metabolism (MESH:D052439), death (MESH:D003643), CRC (MESH:D015179), viral infections (MESH:D014777), subarachnoid hemorrhage (MESH:D013345), leukemic (MESH:D007938), atherogenesis (MESH:D050197), arthritis (MESH:D001168), RA (MESH:D001172), metastasis (MESH:D009362), thrombosis (MESH:D013927), joint swelling (MESH:D007592), cytotoxicity (MESH:D064420), ADH (MESH:D006938), osteoporosis (MESH:D010024)
- **Chemicals:** LPS (MESH:D008070), palmitic acid (MESH:D019308), DHA (MESH:D004281), Lipid (MESH:D008055), 25-hydroxycholesterol (MESH:C007997), diols (MESH:D011276), sterols (MESH:D013261), Fluvastatin (MESH:D000077340), Pioglitazone (MESH:D000077205), taurine (MESH:D013654), TUDCA (MESH:C031655), LXB4 (MESH:C042651), m6A (MESH:C005955), ATP (MESH:D000255), citrate (MESH:D019343), UDCA (MESH:D014580), thioglycollate (MESH:D013864), sodium butyrate (MESH:D020148), glutamine (MESH:D005973), 5-azacytidine (MESH:D001374), Vascepa (MESH:C035276), Glucose (MESH:D005947), elafibranor (MESH:C585906), rosuvastatin (MESH:D000068718), SCFA (MESH:D005232), calcium (MESH:D002118), Acetate (MESH:D000085), Sphingolipids (MESH:D013107), oleic acid (MESH:D019301), HCA (MESH:C004821), DAG (MESH:D004075), Simvastatin (MESH:D019821), alogliptin (MESH:C520853), imiquimod (MESH:D000077271), gabapentin (MESH:D000077206), PUFA (MESH:D005231), gangliosides (MESH:D005732), FTY720 (MESH:D000068876), Atorvastatin (MESH:D000069059), firsocostat (MESH:C000629250), trans-oleic acid (MESH:C011459), ROS (MESH:D000077154), glycerol (MESH:D005990), EC5026 (MESH:C000717068), RvD2 (MESH:C545423), 8,9-DHET (-), F2-isoprostanes (MESH:D028441), ethanolamine (MESH:D019856), eicosanoids (MESH:D015777), GGPP (MESH:C002963), 5-hydroxyindole-3-acetic acid (MESH:D006897), BA (MESH:D001647), valproic acid (MESH:D014635), CDCA (MESH:D002635), cholesterol esters (MESH:D002788), propionate (MESH:D011422), LCA (MESH:D008095), MUFA (MESH:D005229), dapagliflozin (MESH:C529054), phosphocreatine (MESH:D010725)
- **Species:** Bos taurus (bovine, species) [taxon 9913], Gallus gallus (bantam, species) [taxon 9031], Mycobacterium tuberculosis variant bovis BCG (no rank) [taxon 33892], Homo sapiens (human, species) [taxon 9606], Helicobacter pylori (species) [taxon 210], Rattus norvegicus (brown rat, species) [taxon 10116], Bacteroides (genus) [taxon 816], Arctica islandica (species) [taxon 59239], Citrobacter rodentium (species) [taxon 67825], Human immunodeficiency virus 1 (no rank) [taxon 11676], Trypanosoma cruzi (species) [taxon 5693], Histoplasma capsulatum (species) [taxon 5037], Saccharomyces cerevisiae (baker's yeast, species) [taxon 4932], Mus musculus (house mouse, species) [taxon 10090], Caenorhabditis elegans (species) [taxon 6239]
- **Mutations:** rs1800777, V405
- **Cell lines:** TRM — Homo sapiens (Human), Transformed cell line (CVCL_G709), BMDM1 — Mus musculus (Mouse), Transformed cell line (CVCL_C0MS), gammadelta-T — Homo sapiens (Human), Esophageal squamous cell carcinoma, Cancer cell line (CVCL_3174)

## Figures

7 figures with captions in the complete paper: https://tomesphere.com/paper/PMC12907296/full.md

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Source: https://tomesphere.com/paper/PMC12907296