# Maternal docosahexaenoic acid and eicosapentaenoic acid supplementation: effects and mechanisms on lipid metabolism in the offspring **Authors:** Chuhan Shao, Hanmo Lin, Jie Yu, Haiyan Chen, Yaolin Ren, Jing Ren, Yuan Zeng, Yifan Wu, Qian Zhang, Xinhua Xiao PMC · DOI: 10.3389/fnut.2026.1745358 · Frontiers in Nutrition · 2026-02-19 ## TL;DR This review explores how maternal DHA and EPA supplementation during pregnancy and breastfeeding affects lipid metabolism in offspring and the mechanisms behind these effects. ## Contribution The paper provides a narrative review of how maternal DHA and EPA supplementation influences lipid metabolism and related disorders in offspring. ## Key findings - Maternal DHA and EPA supplementation may regulate lipid metabolism-related genes in offspring liver and adipose tissues. - These nutrients can alter the intestinal microbial composition in offspring, impacting lipid metabolic disorders. - The review highlights the potential of prenatal and breastfeeding DHA/EPA intervention to prevent dyslipidemia and obesity in offspring. ## Abstract Environmental factors, such as nutrition, hormones, and metabolites, which are present in early stages of life, have long-lasting effects throughout an organism’s lifespan, and an abnormal nutritional environment throughout gestation and lactation may significantly increase the possibility that offspring will develop chronic metabolic disorders. The important nutrients docosahexaenoic acid (C22:6n-3, DHA) and eicosapentaenoic acid (C20:5n-3, EPA), which are essential long-chain omega-3 polyunsaturated fatty acids, contribute to proper neurological and retinal development and exhibit both anti-inflammatory properties and lipid-reducing capabilities. Recent research has demonstrated that maternal diets supplemented with EPA and DHA may regulate lipid metabolism-related genes in the liver and adipose tissues and alter the intestinal microbial composition in offspring. These changes influence the progression of lipid metabolic disorders, including dyslipidemia, obesity, and MAFLD in the next generation. This narrative review illustrates the effects of maternal EPA and DHA intervention during the prenatal and breastfeeding period on lipid metabolism in the offspring and the underlying mechanisms. We also explore the directions for future research. ## Linked entities - **Chemicals:** docosahexaenoic acid (PubChem CID 445580), eicosapentaenoic acid (PubChem CID 5282847), C22:6n-3 (PubChem CID 445580), DHA (PubChem CID 15608515), C20:5n-3 (PubChem CID 446284), EPA (PubChem CID 446284) - **Diseases:** dyslipidemia (MONDO:0002525), obesity (MONDO:0011122) ## Full-text entities - **Genes:** REG3G (regenerating family member 3 gamma) [NCBI Gene 130120] {aka LPPM429, PAP IB, PAP-1B, PAP1B, PAPIB, REG III}, ZIC1 (Zic family zinc finger 1) [NCBI Gene 7545] {aka BAIDCS, CRS6, ZIC, ZNF201}, ISYNA1 (inositol-3-phosphate synthase 1) [NCBI Gene 51477] {aka INO1, INOS, IPS, IPS 1, IPS-1}, FOXA2 (forkhead box A2) [NCBI Gene 3170] {aka HNF-3-beta, HNF3B, TCF3B}, SCD (stearoyl-CoA desaturase) [NCBI Gene 6319] {aka FADS5, MSTP008, SCD1, SCDOS, hSCD1}, ALPI (alkaline phosphatase, intestinal) [NCBI Gene 248] {aka IAP}, FGF21 (fibroblast growth factor 21) [NCBI Gene 26291], FAS (Fas cell surface death receptor) [NCBI Gene 355] {aka ALPS1A, APO-1, APT1, CD95, FAS1, FASTM}, PRKAA1 (protein kinase AMP-activated catalytic subunit alpha 1) [NCBI Gene 5562] {aka AMPK, AMPK alpha 1, AMPKa1}, SLC5A1 (solute carrier family 5 member 1) [NCBI Gene 6523] {aka D22S675, NAGT, SGLT-1, SGLT1}, PPARA (peroxisome proliferator activated receptor alpha) [NCBI Gene 5465] {aka NR1C1, PPAR, PPAR-alpha, PPARalpha, hPPAR}, SLC17A5 (solute carrier family 17 member 5) [NCBI Gene 26503] {aka AST, ISSD, NSD, SD, SIALIN, SIASD}, MTOR (mechanistic target of rapamycin kinase) [NCBI Gene 2475] {aka FRAP, FRAP1, FRAP2, RAFT1, RAPT1, SKS}, ACADM (acyl-CoA dehydrogenase medium chain) [NCBI Gene 34] {aka ACAD1, MCAD, MCADH}, FASN (fatty acid synthase) [NCBI Gene 2194] {aka FAS, OA-519, SDR27X1}, ACADL (acyl-CoA dehydrogenase long chain) [NCBI Gene 33] {aka ACAD4, LCAD}, MLXIPL (MLX interacting protein like) [NCBI Gene 51085] {aka CHREBP, MIO, MONDOB, WBSCR14, WS-bHLH, bHLHd14}, MAPK8 (mitogen-activated protein kinase 8) [NCBI Gene 5599] {aka JNK, JNK-46, JNK1, JNK1A2, JNK21B1/2, PRKM8}, HMGCR (3-hydroxy-3-methylglutaryl-CoA reductase) [NCBI Gene 3156] {aka LDLCQ3, LGMDR28, MYPLG}, STAMBP (STAM binding protein) [NCBI Gene 10617] {aka AMSH, MICCAP}, TJP1 (tight junction protein 1) [NCBI Gene 7082] {aka ZO-1}, GH1 (growth hormone 1) [NCBI Gene 2688] {aka GH, GH-N, GHB5, GHN, IGHD1A, IGHD1B}, SLC2A2 (solute carrier family 2 member 2) [NCBI Gene 6514] {aka GLUT2}, RETNLB (resistin like beta) [NCBI Gene 84666] {aka FIZZ1, FIZZ2, HXCP2, RELM-beta, RELMb, RELMbeta}, HMGCS1 (3-hydroxy-3-methylglutaryl-CoA synthase 1) [NCBI Gene 3157] {aka CMYO28, HMGCS}, LOX (lysyl oxidase) [NCBI Gene 4015] {aka AAT10}, CIDEA (cell death inducing DFFA like effector a) [NCBI Gene 1149] {aka CIDE-A}, LEP (leptin) [NCBI Gene 3952] {aka LEPD, OB, OBS}, RXRA (retinoid X receptor alpha) [NCBI Gene 6256] {aka NR2B1, RXR-alpha, RXRalpha}, ACACA (acetyl-CoA carboxylase alpha) [NCBI Gene 31] {aka ACAC, ACACAD, ACACalpha, ACC, ACC1, ACCA}, CPT2 (carnitine palmitoyltransferase 2) [NCBI Gene 1376] {aka CPT1, CPTASE, IIAE4}, HMGCS2 (3-hydroxy-3-methylglutaryl-CoA synthase 2) [NCBI Gene 3158], IKBKB (inhibitor of nuclear factor kappa B kinase subunit beta) [NCBI Gene 3551] {aka IKK-2, IKK-beta, IKK2, IKKB, IMD15, IMD15A}, LIPE (lipase E, hormone sensitive type) [NCBI Gene 3991] {aka AOMS4, FPLD6, HSL, LHS, REH}, GGT1 (gamma-glutamyltransferase 1) [NCBI Gene 2678] {aka CD224, D22S672, D22S732, GGT, GGT 1, GGTD}, POMC (proopiomelanocortin) [NCBI Gene 5443] {aka ACTH, CLIP, LPH, MSH, NPP, OBAIRH}, PNPLA2 (patatin like domain 2, triacylglycerol lipase) [NCBI Gene 57104] {aka 1110001C14Rik, ATGL, FP17548, PEDF-R, TTS-2.2, TTS2}, ACADVL (acyl-CoA dehydrogenase very long chain) [NCBI Gene 37] {aka ACAD6, LCACD, VLCAD}, CNR1 (cannabinoid receptor 1) [NCBI Gene 1268] {aka CANN6, CB-R, CB1, CB1A, CB1K5, CB1R}, FADS2 (fatty acid desaturase 2) [NCBI Gene 9415] {aka D6D, DES6, FADSD6, LLCDL2, SLL0262, TU13}, PLIN1 (perilipin 1) [NCBI Gene 5346] {aka FPLD4, PERI, PLIN}, JUNB (JunB proto-oncogene, AP-1 transcription factor subunit) [NCBI Gene 3726] {aka AP-1}, MGLL (monoglyceride lipase) [NCBI Gene 11343] {aka HU-K5, HUK5, MAGL, MGL}, PPARG (peroxisome proliferator activated receptor gamma) [NCBI Gene 5468] {aka CIMT1, FPLD3, GLM1, NR1C3, PPARG1, PPARG2}, UCP1 (uncoupling protein 1) [NCBI Gene 7350] {aka SLC25A7, UCP}, KLK15 (kallikrein related peptidase 15) [NCBI Gene 55554] {aka ACO, HSRNASPH}, COX8A (cytochrome c oxidase subunit 8A) [NCBI Gene 1351] {aka COX, COX8, COX8-2, COX8L, MC4DN15, VIII}, BAAT (bile acid-CoA:amino acid N-acyltransferase) [NCBI Gene 570] {aka BACAT, BACD1, BAT, FHCA3, HCHO}, TMEM26 (transmembrane protein 26) [NCBI Gene 219623], COX2 (cytochrome c oxidase subunit II) [NCBI Gene 4513] {aka COII, MTCO2}, INS (insulin) [NCBI Gene 3630] {aka IDDM, IDDM1, IDDM2, ILPR, IRDN, MODY10}, Adipoq (adiponectin, C1Q and collagen domain containing) [NCBI Gene 11450] {aka 30kDa, APN, Acdc, Acrp30, Ad, Adid}, CCL2 (C-C motif chemokine ligand 2) [NCBI Gene 6347] {aka GDCF-2, HC11, HSMCR30, MCAF, MCP-1, MCP1}, ARRB2 (arrestin beta 2) [NCBI Gene 409] {aka ARB2, ARR2, BARR2}, DIO2 (iodothyronine deiodinase 2) [NCBI Gene 1734] {aka 5DII, D2, DIOII, SELENOY, SelY, TXDI2}, TAB1 (TGF-beta activated kinase 1 (MAP3K7) binding protein 1) [NCBI Gene 10454] {aka 3'-Tab1, MAP3K7IP1}, DGAT2 (diacylglycerol O-acyltransferase 2) [NCBI Gene 84649] {aka ARAT, GS1999FULL, HMFN1045}, AGRP (agouti related neuropeptide) [NCBI Gene 181] {aka AGRT, ART, ASIP2}, Fads2 (fatty acid desaturase 2) [NCBI Gene 83512] {aka Fadsd6}, GGTLC5P (gamma-glutamyltransferase light chain 5 pseudogene) [NCBI Gene 653590] {aka GGT} - **Diseases:** insulin resistance (MESH:D007333), weight loss (MESH:D015431), preterm birth (MESH:D047928), abnormal lipid metabolism (MESH:D052439), endotoxemia (MESH:D019446), LBW (MESH:D001724), hypertriglyceridemia (MESH:D015228), cognitive decline (MESH:D003072), abdominal obesity (MESH:D056128), liver injury (MESH:D017093), adiposity (MESH:D018205), type 2 diabetes (MESH:D003924), gut dysbiosis (MESH:D064806), diabetes mellitus (MESH:D003920), Alzheimer's disease (MESH:D000544), NAFLD (MESH:D065626), mitochondrial damage (MESH:D028361), Dyslipidemia (MESH:D050171), fibrosis (MESH:D005355), metabolic syndrome (MESH:D024821), Disease (MESH:D004194), HL (MESH:C538324), inflammation (MESH:D007249), hypoxia (MESH:D000860), metabolic dysregulation (MESH:D021081), metabolic diseases (MESH:D008659), overweight (MESH:D050177), gestational diabetes (MESH:D016640), Obesity (MESH:D009765), MAFLD (MESH:D005234) - **Chemicals:** carbohydrate (MESH:D002241), fatty acid (MESH:D005227), homocysteine (MESH:D006710), PUFA (MESH:D005231), eicosatetraenoic acid (MESH:D001095), 2-arachidonoylglycerol (MESH:C094503), 20:4n-3 (-), eicosanoid (MESH:D015777), olive oil (MESH:D000069463), SCFA (MESH:D005232), FA (MESH:D005492), DHA (MESH:C027493), Glucose (MESH:D005947), PFO (MESH:C076994), dopamine (MESH:D004298), endocannabinoid (MESH:D063388), LPS (MESH:D008070), DHA (MESH:D004281), lipid (MESH:D008055), fructose (MESH:D005632), ALA (MESH:D000409), TG (MESH:D014280), prostaglandin (MESH:D011453), N-3 PUFAs (MESH:D015525), 18:4n-3 (MESH:C062895), 22:5n-3 (MESH:C026219), TGs (MESH:C026285), Cho (MESH:C034482), cAMP (MESH:D000242), cholesterol (MESH:D002784), PGF2alpha (MESH:D015237), fish oil (MESH:D005395), anandamide (MESH:C078814), PGE2 (MESH:D015232), FFA (MESH:D005230), arachidonic acid (MESH:D016718), 18:3n-3 (MESH:D017962), C20:5n-3 (MESH:D015118) - **Species:** Homo sapiens (human, species) [taxon 9606], Barnesiella (genus) [taxon 397864], Rattus norvegicus (brown rat, species) [taxon 10116], Alistipes (genus) [taxon 239759], Lactobacillus (genus) [taxon 1578], Mus musculus (house mouse, species) [taxon 10090], Acetatifactor (genus) [taxon 1427378], Ruminococcus (genus) [taxon 1263], Desulfovibrio (genus) [taxon 872] - **Cell lines:** C57BL/6J — Mus musculus (Mouse), Transformed cell line (CVCL_C0MW) ## Full text _Full body text omitted from this summary view._ Fetch the complete paper as Markdown: https://tomesphere.com/paper/PMC12960546/full.md ## Figures 4 figures with captions in the complete paper: https://tomesphere.com/paper/PMC12960546/full.md ## References 139 references — full list in the complete paper: https://tomesphere.com/paper/PMC12960546/full.md --- Source: https://tomesphere.com/paper/PMC12960546