# Immunometabolism in obesity: Understanding the beneficial and detrimental roles of inflammation

**Authors:** Yun Sok Lee

PMC · DOI: 10.1371/journal.pbio.3003620 · 2026-01-21

## TL;DR

The paper explores how inflammation in obesity can both help and harm metabolic health, depending on its stage.

## Contribution

It highlights the dual, context-dependent role of metaflammation in obesity, emphasizing its initially adaptive function.

## Key findings

- Metaflammation can support metabolic homeostasis in early obesity.
- Chronic metaflammation leads to insulin resistance and metabolic dysfunction.
- The transition from beneficial to harmful inflammation is a key focus.

## Abstract

In obesity, nutrient excess and altered adipocyte secretory profiles reprogram cell-intrinsic metabolism, leading to the activation of immune cells within metabolically active tissues such as adipose tissue. This obesity-associated chronic low-grade metabolic inflammation (often referred to as metaflammation) is a well-established driver of insulin resistance and metabolic dysfunction. However, several lines of emerging evidence suggest that metaflammation is not merely a pathologic process, but may also serve as an adaptive response that supports metabolic homeostasis, particularly at the early stages of obesity. This Essay discusses immunometabolic mechanisms underlying the dual nature of metaflammation in obesity, highlighting how its initially beneficial effects can transition into detrimental outcomes.

Chronic low-grade metabolic inflammation (known as metaflammation) drives insulin resistance and metabolic dysfunction in obesity. This Essay discusses the immunometabolic mechanisms underlying metaflammation with a focus on its lesser known beneficial effects and how they can transition into detrimental outcomes.

## Linked entities

- **Diseases:** obesity (MONDO:0011122)

## Full-text entities

- **Genes:** Tfeb (transcription factor EB) [NCBI Gene 21425] {aka Tcfeb, bHLHe35}, Slc25a5 (solute carrier family 25 (mitochondrial carrier, adenine nucleotide translocator), member 5) [NCBI Gene 11740] {aka Ant2}, Abca1 (ATP-binding cassette, sub-family A member 1) [NCBI Gene 11303] {aka ABC-1, Abc1}, Il10 (interleukin 10) [NCBI Gene 16153] {aka CSIF, If2a, Il-10}, Lamb2 (laminin, beta 2) [NCBI Gene 16779] {aka Lamb-2, Lams, npht}, Sema3e (sema domain, immunoglobulin domain (Ig), short basic domain, secreted, (semaphorin) 3E) [NCBI Gene 20349] {aka 6430702L12, Semah, mKIAA0331}, Pdk1 (pyruvate dehydrogenase kinase, isoenzyme 1) [NCBI Gene 228026] {aka B830012B01, D530020C15Rik}, Mir210 (microRNA 210) [NCBI Gene 387206] {aka Mirn210, mir-210, mmu-mir-210}, Gpx1 (glutathione peroxidase 1) [NCBI Gene 14775] {aka CGPx, GPx-1, GSHPx-1, Gpx}, Nup62 (nucleoporin 62) [NCBI Gene 18226] {aka D7Ertd649e, Nupc1, p62}, Slc2a1 (solute carrier family 2 (facilitated glucose transporter), member 1) [NCBI Gene 20525] {aka GT1, Glut-1, Glut1, M100200, Rgsc200}, Siglec1 (sialic acid binding Ig-like lectin 1, sialoadhesin) [NCBI Gene 20612] {aka Cd169, Siglec-1, Sn}, Atm (ataxia telangiectasia mutated) [NCBI Gene 11920] {aka C030026E19Rik}, Fasn (fatty acid synthase) [NCBI Gene 14104] {aka A630082H08Rik, FAS}, Trem2 (triggering receptor expressed on myeloid cells 2) [NCBI Gene 83433] {aka TREM-2, Trem2a, Trem2b, Trem2c}, Cd14 (CD14 antigen) [NCBI Gene 12475], Lamp2 (lysosomal-associated membrane protein 2) [NCBI Gene 16784] {aka CD107b, LGP-B, Lamp II, Lamp-2, Lamp-2a, Lamp-2b}, Cat (catalase) [NCBI Gene 12359] {aka 2210418N07, Cas-1, Cas1, Cs-1}, Tfrc (transferrin receptor) [NCBI Gene 22042] {aka 2610028K12Rik, CD71, E430033M20Rik, Mtvr1, TFR, TFR1}, Sat1 (spermidine/spermine N1-acetyl transferase 1) [NCBI Gene 20229] {aka SSAT, Sat}, Il6 (interleukin 6) [NCBI Gene 16193] {aka Il-6}, Mir690 (microRNA 690) [NCBI Gene 751543] {aka Mirn690, mir-690, mmu-mir-690}, Dpp4 (dipeptidylpeptidase 4) [NCBI Gene 13482] {aka Cd26, Dpp-4, THAM}, Nos2 (nitric oxide synthase 2, inducible) [NCBI Gene 18126] {aka MAC-NOS, NOS-II, Nos-2, Nos2a, i-NOS, iNOS}, Gpx3 (glutathione peroxidase 3) [NCBI Gene 14778] {aka EGPx, GPx, GSHPx-3, GSHPx-P}, Ngf (nerve growth factor) [NCBI Gene 18049] {aka Ngfb, beta-NGF}, Ccl5 (C-C motif chemokine ligand 5) [NCBI Gene 20304] {aka MuRantes, RANTES, SISd, Scya5, TCP228}, Mir155 (microRNA 155) [NCBI Gene 387173] {aka Mirn155, mir-155, mmu-mir-155}, Mrc1 (mannose receptor, C type 1) [NCBI Gene 17533] {aka CD206, MR}, 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}, Ccl8 (C-C motif chemokine ligand 8) [NCBI Gene 20307] {aka 1810063B20Rik, HC14, MCP-2, Mcp2, Scya8}, Cxcl12 (C-X-C motif chemokine ligand 12) [NCBI Gene 20315] {aka Pbsf, Scyb12, Sdf1, Tlsf, Tpar1}, Mtor (mechanistic target of rapamycin kinase) [NCBI Gene 56717] {aka 2610315D21Rik, FRAP, FRAP2, Frap1, RAFT1, RAPT1}, Chrna2 (cholinergic receptor nicotinic alpha 2 subunit) [NCBI Gene 110902] {aka Acra-2, Acra2}, Cybb (cytochrome b-245, beta polypeptide) [NCBI Gene 13058] {aka CGD91-phox, Cgd, Cyd, Nox2, gp91-1, gp91phox}, Itgax (integrin alpha X) [NCBI Gene 16411] {aka Cd11c, Cr4, N418}, Slc2a4 (solute carrier family 2 (facilitated glucose transporter), member 4) [NCBI Gene 20528] {aka GT2, Glut-4, Glut4, twgy}, Nod1 (nucleotide-binding oligomerization domain containing 1) [NCBI Gene 107607] {aka C230079P11, Card4, F830007N14Rik, Nlrc1, mNod1}, Chat (choline O-acetyltransferase) [NCBI Gene 12647] {aka B230380D24Rik, CHOACTase}, Epas1 (endothelial PAS domain protein 1) [NCBI Gene 13819] {aka HIF-2alpha, HIF2A, HLF, HRF, MOP2, bHLHe73}, Tlr9 (toll-like receptor 9) [NCBI Gene 81897], Il4 (interleukin 4) [NCBI Gene 16189] {aka BSF-1, Il-4}, Ccl2 (C-C motif chemokine ligand 2) [NCBI Gene 20296] {aka HC11, JE, MCAF, MCP-1, MCP1, SMC-CF}, Ctsk (cathepsin K) [NCBI Gene 13038] {aka MMS10-Q, Ms10q, catK}, Serpine1 (serine (or cysteine) peptidase inhibitor, clade E, member 1) [NCBI Gene 18787] {aka PAI-1, PAI1, Planh1}, S100a1 (S100 calcium binding protein A1) [NCBI Gene 20193] {aka S100, S100a}, Flcn (folliculin) [NCBI Gene 216805] {aka B430214A04Rik, Bhd, FLCL}, Ccr2 (C-C motif chemokine receptor 2) [NCBI Gene 12772] {aka Cc-ckr-2, Ccr2a, Ccr2b, Ckr2, Ckr2a, Ckr2b}, Xbp1 (X-box binding protein 1) [NCBI Gene 22433] {aka D11Ertd39e, TREB-5, TREB5, XBP-1}, Cd9 (CD9 antigen) [NCBI Gene 12527] {aka Tspan29}, Vegfa (vascular endothelial growth factor A) [NCBI Gene 22339] {aka L-VEGF, Vegf, Vpf}, Rag1 (recombination activating 1) [NCBI Gene 19373] {aka Rag-1}, Adipoq (adiponectin, C1Q and collagen domain containing) [NCBI Gene 11450] {aka 30kDa, APN, Acdc, Acrp30, Ad, Adid}, INS (insulin) [NCBI Gene 3630] {aka IDDM, IDDM1, IDDM2, ILPR, IRDN, MODY10}, Timd4 (T cell immunoglobulin and mucin domain containing 4) [NCBI Gene 276891] {aka B430010N18Rik, TIM-4, Tim4}, Acp5 (acid phosphatase 5, tartrate resistant) [NCBI Gene 11433] {aka TRACP, TRAP}, Tm4sf19 (transmembrane 4 L six family member 19) [NCBI Gene 277203] {aka EG277203}, Nox4 (NADPH oxidase 4) [NCBI Gene 50490], Lep (leptin) [NCBI Gene 16846] {aka ob, obese}, Mir615 (microRNA 615) [NCBI Gene 751557] {aka Mir, Mirn615, mir-615, mmu-mir-615}
- **Diseases:** beta cell dysfunction (MESH:D007340), Obesity (MESH:D009765), Weight regain (MESH:D055191), Iron overload (MESH:D019190), mitochondrial dysfunction (MESH:D028361), infection (MESH:D007239), tissue (MESH:D017695), hyperinsulinemia (MESH:D006946), liver pseudohypoxia (MESH:D017093), hyperglycemia (MESH:D006943), vascular dysfunction (MESH:D002561), T2D (MESH:D003924), hypoxic (MESH:D002534), fibrosis (MESH:D005355), diabetes (MESH:D003920), metabolic syndrome (MESH:D024821), glucose (MESH:D018149), impaired glycemic control (MESH:D007174), insulin intolerance (MESH:D007333), atherosclerosis (MESH:D050197), cardiovascular disease (MESH:D002318), MASLD (MESH:D008107), hypoxia (MESH:D000860), weight loss (MESH:D015431), gut dysbiosis (MESH:D064806), necrosis (MESH:D009336), HFD (MESH:D004620), adipocyte hypertrophy (MESH:D006984), adipose (MESH:D018205), MASH (MESH:D005234), dyslipidemia (MESH:D050171), metabolic abnormalities (MESH:D008659), adipose tissue inflammation (MESH:D007249), weight gain (MESH:D015430)
- **Chemicals:** fatty acids (MESH:D005227), lipid (MESH:D008055), leukotriene B4 (MESH:D007975), phosphatidylethanolamine (MESH:C483858), salicylic acid (MESH:D020156), ACh (MESH:D000109), glucose (MESH:D005947), rosiglitazone (MESH:D000077154), NO (MESH:D009569), catecholamine (MESH:D002395), Ca2+ (-), metal (MESH:D008670), uric acid (MESH:D014527), Iron (MESH:D007501), fat (MESH:D005223), FFA (MESH:D005230), lactate (MESH:D019344), omega-3 fatty acids (MESH:D015525), thiazolidinediones (MESH:D045162), ceramide (MESH:D002518), ATP (MESH:D000255), ROS (MESH:D017382), phosphatidylcholine (MESH:D010713), oxygen (MESH:D010100), DHA (MESH:C027493), blood glucose (MESH:D001786), cholesterol (MESH:D002784), oligonucleotides (MESH:D009841), LPS (MESH:D008070), clodronate (MESH:D004002), palmitic acid (MESH:D019308), NE (MESH:D009638)
- **Species:** Mus musculus (house mouse, species) [taxon 10090], Homo sapiens (human, species) [taxon 9606]

## Figures

2 figures with captions in the complete paper: https://tomesphere.com/paper/PMC12854482/full.md

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Source: https://tomesphere.com/paper/PMC12854482