# Macrophage migration inhibitory factor from nematode parasite as a novel approach to combat obesity and its metabolic complications

**Authors:** Mi-Kyung Park, MinKyoung Cho, Hak Sun Yu

PMC · DOI: 10.3389/fimmu.2026.1742993 · Frontiers in Immunology · 2026-02-05

## TL;DR

This study explores a protein from a nematode parasite that may help reduce obesity and its related health issues by targeting fat formation and inflammation.

## Contribution

The study introduces a novel therapeutic approach using a nematode-derived protein to combat obesity and its metabolic complications.

## Key findings

- rAs-MIF reduced lipid accumulation and inhibited adipogenesis in 3T3-L1 cells.
- In mice, rAs-MIF decreased body weight and improved glucose tolerance while modulating immune responses.
- The protein activated brown fat and suppressed white fat lipid synthesis in high-fat diet-fed mice.

## Abstract

Obesity is a complex chronic disease characterized by excessive fat accumulation, dysregulation of energy homeostasis, and associated mild inflammation, significantly increasing the risk of metabolic diseases, cardiovascular diseases, and other chronic diseases. Addressing this requires innovative approaches targeting the underlying mechanisms. This study investigates the therapeutic effects of Anisakis simplex-derived macrophage migration inhibitory factor (1) on adipogenesis, lipid metabolism, and inflammation in high-fat diet (2)-induced obesity.

We evaluated the effects of rAs-MIF on adipocyte differentiation, lipid droplet formation, and expression of adipogenic and inflammatory genes in 3T3-L1 cells. In addition, we investigated the effects of orally administered rAs-MIF on lipid accumulation, glucose metabolism, serum biochemical markers, and immune regulation in mice fed a 45% high-fat diet.

rAs-MIF dose-dependently reduced lipid droplet size and triglyceride accumulation, inhibited adipogenesis and inflammatory gene expression, and upregulated adiponectin levels in 3T3-L1 cells. In HFD-fed mice, rAs-MIF decreased body weight gain, fat mass, and serum lipid levels, enhanced glucose tolerance, and activated interscapular brown adipose tissue while suppressing epididymal white adipose tissue lipid synthesis. Moreover, it modulated the immune balance by promoting the polarization of anti-inflammatory macrophages and reducing the production of pro-inflammatory cytokines.

rAs-MIF demonstrates a dual regulatory effect on adipogenesis and metabolism, highlighting its potential as a therapeutic candidate for obesity.

## Linked entities

- **Diseases:** obesity (MONDO:0011122)
- **Species:** Anisakis simplex (taxon 6269), Mus musculus (taxon 10090)

## Full-text entities

- **Genes:** Map3k14 (mitogen-activated protein kinase kinase kinase 14) [NCBI Gene 53859] {aka Nik, aly}, IL10 (interleukin 10) [NCBI Gene 3586] {aka CSIF, GVHDS, IL-10, IL10A, TGIF}, Pparg (peroxisome proliferator activated receptor gamma) [NCBI Gene 19016] {aka Nr1c3, PPAR-gamma, PPAR-gamma2, PPARgamma, PPARgamma2}, Il1b (interleukin 1 beta) [NCBI Gene 16176] {aka IL-1beta, Il-1b}, Igkv1-122 (immunoglobulin kappa chain variable 1-122) [NCBI Gene 434024] {aka Gm16798, bl1}, STAT6 (signal transducer and activator of transcription 6) [NCBI Gene 6778] {aka D12S1644, HIES6, IL-4-STAT, STAT6B, STAT6C}, Itgax (integrin alpha X) [NCBI Gene 16411] {aka Cd11c, Cr4, N418}, Apc (APC, WNT signaling pathway regulator) [NCBI Gene 11789] {aka CC1, Min, mAPC}, Adipoq (adiponectin, C1Q and collagen domain containing) [NCBI Gene 11450] {aka 30kDa, APN, Acdc, Acrp30, Ad, Adid}, Mrc1 (mannose receptor, C type 1) [NCBI Gene 17533] {aka CD206, MR}, Ifng (interferon gamma) [NCBI Gene 15978] {aka IFN-g, If2f, Ifg}, Ppargc1a (peroxisome proliferative activated receptor, gamma, coactivator 1 alpha) [NCBI Gene 19017] {aka A830037N07Rik, Gm11133, PGC-1, PPARGC-1-alpha, Pgc-1alpha, Pgc1}, NFKB1 (nuclear factor kappa B subunit 1) [NCBI Gene 4790] {aka CVID12, EBP-1, KBF1, NF-kB, NF-kB1, NF-kappa-B1}, Lep (leptin) [NCBI Gene 16846] {aka ob, obese}, Itgam (integrin alpha M) [NCBI Gene 16409] {aka CD11b/CD18, CR3, CR3A, Cd11b, F730045J24Rik, Ly-40}, Fabp4 (fatty acid binding protein 4, adipocyte) [NCBI Gene 11770] {aka 422/aP2, AFABP, ALBP, ALBP/Ap2, Ap2, Lbpl}, Il6 (interleukin 6) [NCBI Gene 16193] {aka Il-6}, Slc2a4 (solute carrier family 2 (facilitated glucose transporter), member 4) [NCBI Gene 20528] {aka GT2, Glut-4, Glut4, twgy}, Mgl2 (macrophage galactose N-acetyl-galactosamine specific lectin 2) [NCBI Gene 216864] {aka CD301b}, Tgfb1 (transforming growth factor, beta 1) [NCBI Gene 21803] {aka TGF-beta1, TGFbeta1, Tgfb, Tgfb-1}, Tnf (tumor necrosis factor) [NCBI Gene 21926] {aka DIF, TNF-a, TNF-alpha, TNFSF2, TNFalpha, Tnfa}, Ucp1 (uncoupling protein 1 (mitochondrial, proton carrier)) [NCBI Gene 22227] {aka Slc25a7, Ucp}, Il10 (interleukin 10) [NCBI Gene 16153] {aka CSIF, If2a, Il-10}, TGFB1 (transforming growth factor beta 1) [NCBI Gene 7040] {aka CAEND1, CED, DPD1, IBDIMDE, LAP, TGF-beta1}, Slc10a2 (solute carrier family 10, member 2) [NCBI Gene 20494] {aka 9130221J18Rik, ASBT, IBAT, ISBT}, MRC1 (mannose receptor C-type 1) [NCBI Gene 4360] {aka CD206, CLEC13D, CLEC13DL, MMR, MRC1L1, bA541I19.1}, Asc1 (anterior suture cataract 1) [NCBI Gene 104385] {aka Asc-1}, Ptprc (protein tyrosine phosphatase receptor type C) [NCBI Gene 19264] {aka B220, CD45R, Cd45, L-CA, Ly-5, Lyt-4}, IL13 (interleukin 13) [NCBI Gene 3596] {aka IL-13, P600}, PPARG (peroxisome proliferator activated receptor gamma) [NCBI Gene 5468] {aka CIMT1, FPLD3, GLM1, NR1C3, PPARG1, PPARG2}, Gapdh (glyceraldehyde-3-phosphate dehydrogenase) [NCBI Gene 14433] {aka Gapd}, Ppara (peroxisome proliferator activated receptor alpha) [NCBI Gene 19013] {aka 4933429D07Rik, Nr1c1, PPAR-alpha, PPARalpha, Ppar}, IL4 (interleukin 4) [NCBI Gene 3565] {aka BCGF-1, BCGF1, BSF-1, BSF1, IL-4}, Hoxc9 (homeobox C9) [NCBI Gene 15427] {aka Hox-3.2}, MIF (macrophage migration inhibitory factor) [NCBI Gene 4282] {aka GIF, GLIF, MMIF}, Cebpa (CCAAT/enhancer binding protein alpha) [NCBI Gene 12606] {aka C/ebpalpha, CBF-A, Cebp}, Mif (macrophage migration inhibitory factor (glycosylation-inhibiting factor)) [NCBI Gene 17319] {aka DER6, GIF, Glif}
- **Diseases:** metabolic syndrome (MESH:D024821), hyperlipidemia (MESH:D006949), fibrosis (MESH:D005355), Chronic inflammation (MESH:D007249), non-alcoholic fatty liver disease (MESH:D065626), -induced obesity (MESH:D009765), autoimmune and metabolic disease (MESH:D001327), weight gain (MESH:D015430), hepatic steatosis (MESH:D005234), metabolic diseases (MESH:D008659), insulin resistance (MESH:D007333), weight loss (MESH:D015431), adipocyte hypertrophy (MESH:D006984), cardiovascular diseases (MESH:D002318), helminth infection (MESH:D007239), parasite (MESH:D010272), type 2 diabetes (MESH:D003924), chronic diseases (MESH:D002908)
- **Chemicals:** P (MESH:D010758), paraffin (MESH:D010232), fat (MESH:D005223), streptomycin (MESH:D013307), triglyceride (MESH:D014280), Oil Red O (MESH:C011049), TRIzol (MESH:C411644), water (MESH:D014867), Blood glucose (MESH:D001786), cholesterol (MESH:D002784), isopropanol (MESH:D019840), hematoxylin (MESH:D006416), penicillin (MESH:D010406), H&amp;E (MESH:D006371), S (MESH:D013455), ACK (-), fatty acid (MESH:D005227), isobutylmethylxanthine (MESH:D015056), dexamethasone (MESH:D003907), lipid (MESH:D008055), rAs (MESH:D011883), formaldehyde (MESH:D005557), glucose (MESH:D005947), As (MESH:D001151), eosin (MESH:D004801)
- **Species:** Anisakis simplex (herring worm, species) [taxon 6269], Mus musculus (house mouse, species) [taxon 10090], Trichinella spiralis (species) [taxon 6334], Nematoda (nematode, phylum) [taxon 6231], Homo sapiens (human, species) [taxon 9606]
- **Cell lines:** 3T3-L1 — Mus musculus (Mouse), Spontaneously immortalized cell line (CVCL_0123), C57BL/6 — Mus musculus (Mouse), Transformed cell line (CVCL_C0MU)

## Full text

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## Figures

6 figures with captions in the complete paper: https://tomesphere.com/paper/PMC12916604/full.md

## References

61 references — full list in the complete paper: https://tomesphere.com/paper/PMC12916604/full.md

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Source: https://tomesphere.com/paper/PMC12916604