# Two Sides of a Coin: Molecular, metabolic, and Phenotypic Convergence in Pediatric Undernutrition and Obesity

**Authors:** Mercy Eloho Sosanya, Jennifer L. Temple

PMC · DOI: 10.1007/s13679-026-00689-5 · Current Obesity Reports · 2026-03-02

## TL;DR

This review compares the metabolic and molecular effects of childhood undernutrition and obesity, showing how both lead to similar long-term health risks despite different causes.

## Contribution

The paper highlights shared biological pathways and outcomes between pediatric undernutrition and obesity, emphasizing their convergent health impacts.

## Key findings

- Both undernutrition and obesity in childhood are linked to chronic metabolic disorders like insulin resistance and diabetes.
- Shared mechanisms include endocrine, immunological, epigenetic, and gut microbiome pathways.
- Long-term outcomes such as cardiovascular disease and cancer are common to both conditions.

## Abstract

This narrative review juxtaposes the metabolic and molecular consequences of pediatric under- and overnutrition, highlighting the similarities and differences between these two nutritional states occurring simultaneously in different parts of the world.

Numerous biological changes in pediatric acute undernutrition and obesity have been linked to elevated risks of chronic metabolic disorders. We summarize recent evidence on pathophysiological pathways and outcomes common to both conditions. Despite etiological divergence, early-life nutritional imbalances converge on shared mechanisms and consequences with intergenerational implications.

Both acute undernutrition and obesity in childhood have intersecting long-term outcomes including insulin resistance, type 2 diabetes, cardiovascular diseases, hepatic steatosis, cancers, and others, mediated through endocrine, immunological, epigenetic, and gut microbiome pathways, albeit via diverse specific mechanisms. Robust, longitudinal studies in varied geopolitical settings are needed to further elucidate the complex mechanisms, long-term phenotypic consequences, and therapeutic effects in these twin conditions.

## Linked entities

- **Diseases:** type 2 diabetes (MONDO:0005148)

## Full-text entities

- **Genes:** DUSP1 (dual specificity phosphatase 1) [NCBI Gene 1843] {aka CL100, HVH1, MKP-1, MKP1, PTPN10}, GPR166P (G protein-coupled receptor 166, pseudogene) [NCBI Gene 442206] {aka GPCR, PGR9}, NDUFS1 (NADH:ubiquinone oxidoreductase core subunit S1) [NCBI Gene 4719] {aka CI-75Kd, CI-75k, MC1DN5, PRO1304}, VTRNA2-1 (vault RNA 2-1) [NCBI Gene 100126299] {aka CBL-3, CBL3, MIR886, MIRN886, VTRNA2, hsa-mir-886}, INS (insulin) [NCBI Gene 3630] {aka IDDM, IDDM1, IDDM2, ILPR, IRDN, MODY10}, GNAS (GNAS complex locus) [NCBI Gene 2778] {aka AHO, AIMAH1, C20orf45, GNAS1, GPSA, GSA}, NFE2L1 (NFE2 like bZIP transcription factor 1) [NCBI Gene 4779] {aka LCR-F1, NRF-1, NRF1, TCF11}, IGF1 (insulin like growth factor 1) [NCBI Gene 3479] {aka IGF, IGF-I, IGFI, MGF}, IL1B (interleukin 1 beta) [NCBI Gene 3553] {aka IL-1, IL1-BETA, IL1F2, IL1beta}, GCG (glucagon) [NCBI Gene 2641] {aka GLP-1, GLP1, GLP2, GRPP}, TLR4 (toll like receptor 4) [NCBI Gene 7099] {aka ARMD10, CD284, TLR-4, TOLL}, FFAR3 (free fatty acid receptor 3) [NCBI Gene 2865] {aka FFA3R, GPR41}, BOLA2 (bolA family member 2) [NCBI Gene 552900] {aka BOLA2A, My016}, SUV39H1 (SUV39H1 histone lysine methyltransferase) [NCBI Gene 6839] {aka H3-K9-HMTase 1, KMT1A, MG44, SUV39H}, TNF (tumor necrosis factor) [NCBI Gene 7124] {aka DIF, IMD127, TNF-alpha, TNFA, TNFSF2, TNLG1F}, PTPRC (protein tyrosine phosphatase receptor type C) [NCBI Gene 5788] {aka B220, CD45, CD45R, GP180, IMD105, L-CA}, HSD11B1 (hydroxysteroid 11-beta dehydrogenase 1) [NCBI Gene 3290] {aka 11-DH, 11-beta-HSD1, CORTRD2, HDL, HSD11, HSD11B}, IL10 (interleukin 10) [NCBI Gene 3586] {aka CSIF, GVHDS, IL-10, IL10A, TGIF}, SERPINA7 (serpin family A member 7) [NCBI Gene 6906] {aka TBG, TBGQTL}, DDIT3 (DNA damage inducible transcript 3) [NCBI Gene 1649] {aka AltDDIT3, C/EBPzeta, CEBPZ, CHOP, CHOP-10, CHOP10}, PDX1 (pancreatic and duodenal homeobox 1) [NCBI Gene 3651] {aka GSF, IDX-1, IPF1, IUF1, MODY4, PAGEN1}, NR1H3 (nuclear receptor subfamily 1 group H member 3) [NCBI Gene 10062] {aka LXR-a, LXRA, RLD-1}, GGH (gamma-glutamyl hydrolase) [NCBI Gene 8836] {aka GATD10, GH}, IL18 (interleukin 18) [NCBI Gene 3606] {aka IGIF, IL-18, IL-1g, IL1F4}, ADIPOQ (adiponectin, C1Q and collagen domain containing) [NCBI Gene 9370] {aka ACDC, ACRP30, ADIPQTL1, ADPN, APM-1, APM1}, SIRT1 (sirtuin 1) [NCBI Gene 23411] {aka SIR2, SIR2L1, SIR2alpha}, TRIB3 (tribbles pseudokinase 3) [NCBI Gene 57761] {aka C20orf97, NIPK, SINK, SKIP3, TRB3}, MAFA (MAF bZIP transcription factor A) [NCBI Gene 389692] {aka INSDM, RIPE3b1, hMafA}, PCDHGA4 (protocadherin gamma subfamily A, 4) [NCBI Gene 56111] {aka PCDH-GAMMA-A4}, SREBF1 (sterol regulatory element binding transcription factor 1) [NCBI Gene 6720] {aka HMD, IFAP2, SREBP1, bHLHd1}, H3c7 (H3 clustered histone 7) [NCBI Gene 260423] {aka H3.2-221, H3c13, H3c14, H3c15, H3c2, H3c3}, IL12B (interleukin 12B) [NCBI Gene 3593] {aka CLMF, CLMF2, IL-12B, IMD28, IMD29, NKSF}, NFKB1 (nuclear factor kappa B subunit 1) [NCBI Gene 4790] {aka CVID12, EBP-1, KBF1, NF-kB, NF-kB1, NF-kappa-B1}, PTPRN2 (protein tyrosine phosphatase receptor type N2) [NCBI Gene 5799] {aka IA-2beta, IAR, ICAAR, PTPRP, R-PTP-N2}, CXCL8 (C-X-C motif chemokine ligand 8) [NCBI Gene 3576] {aka GCP-1, GCP1, IL8, LECT, LUCT, LYNAP}, PPARGC1A (PPARG coactivator 1 alpha) [NCBI Gene 10891] {aka LEM6, PGC-1(alpha), PGC-1alpha, PGC-1v, PGC1, PGC1A}, IL15 (interleukin 15) [NCBI Gene 3600] {aka IL-15}, TFAM (transcription factor A, mitochondrial) [NCBI Gene 7019] {aka MTDPS15, MTTF1, MTTFA, TCF6, TCF6L1, TCF6L2}, ESAM (endothelial cell adhesion molecule) [NCBI Gene 90952] {aka NEDIHSS, W117m}, TRH (thyrotropin releasing hormone) [NCBI Gene 7200] {aka Pro-TRH, TRF}, PHLDA1 (pleckstrin homology like domain family A member 1) [NCBI Gene 22822] {aka DT1P1B11, PHRIP, TDAG51}, GPX3 (glutathione peroxidase 3) [NCBI Gene 2878] {aka GPx-P, GSHPx-3, GSHPx-P}, FGF21 (fibroblast growth factor 21) [NCBI Gene 26291], TGFB1 (transforming growth factor beta 1) [NCBI Gene 7040] {aka CAEND1, CED, DPD1, IBDIMDE, LAP, TGF-beta1}, NPY (neuropeptide Y) [NCBI Gene 4852] {aka PYY4}, MPO (myeloperoxidase) [NCBI Gene 4353], HDAC9 (histone deacetylase 9) [NCBI Gene 9734] {aka HD7, HD7b, HD9, HDAC, HDAC7B, HDAC9B}, CD8A (CD8 subunit alpha) [NCBI Gene 925] {aka CD8, CD8alpha, IMD116, Leu2, p32}, TTR (transthyretin) [NCBI Gene 7276] {aka AMYLD1, ATTR, CTS, CTS1, HEL111, HsT2651}, FFAR2 (free fatty acid receptor 2) [NCBI Gene 2867] {aka FFA2R, GPR43}, PDGFRB (platelet derived growth factor receptor beta) [NCBI Gene 5159] {aka CD140B, IBGC4, IMF1, JTK12, KOGS, OPDKD}, ALB (albumin) [NCBI Gene 213] {aka FDAHT, HSA, PRO0883, PRO0903, PRO1341}, CSF2 (colony stimulating factor 2) [NCBI Gene 1437] {aka CSF, GMCSF}, SLC2A4 (solute carrier family 2 member 4) [NCBI Gene 6517] {aka GLUT4}, IL6 (interleukin 6) [NCBI Gene 3569] {aka BSF-2, BSF2, CDF, HGF, HSF, IFN-beta-2}, NR1H4 (nuclear receptor subfamily 1 group H member 4) [NCBI Gene 9971] {aka BAR, FXR, HRR-1, HRR1, PFIC5, RIP14}, FASN (fatty acid synthase) [NCBI Gene 2194] {aka FAS, OA-519, SDR27X1}, H4C6 (H4 clustered histone 6) [NCBI Gene 8361] {aka H4, H4/c, H4FC, HIST1H4F}, MAPK8 (mitogen-activated protein kinase 8) [NCBI Gene 5599] {aka JNK, JNK-46, JNK1, JNK1A2, JNK21B1/2, PRKM8}, PAX8 (paired box 8) [NCBI Gene 7849] {aka PAX-8}
- **Diseases:** micronutrient insufficiency (MESH:D000309), cancer (MESH:D009369), Diabetes (MESH:D003920), Dysbiosis (MESH:D064806), endothelial dysfunction (MESH:D014652), height deficits (MESH:C000719188), non-alcoholic fatty liver disease (MESH:D065626), beta-cell failure (MESH:D051437), impaired (MESH:D060825), Under- and Overnutrition (MESH:D044343), pancreatic (MESH:D010195), atrophy (MESH:D001284), edema (MESH:D004487), metabolic disruption (MESH:D019958), cardiometabolic disease (MESH:D024821), fibrosis (MESH:D005355), muscle wasting (MESH:D009133), Inflammatory (MESH:D007249), lipotoxic injury (MESH:D014947), maladies (MESH:C535802), growth faltering (MESH:D006130), mitochondrial dysfunction (MESH:D028361), dyslipidemia (MESH:D050171), acute (MESH:D000208), iron deficiency (MESH:D019337), metabolic damage (MESH:D008659), excessive body weight (MESH:D001835), metabolic dysregulation (MESH:D021081), Enteropathy (MESH:C538273), wasting of skeletal muscles (MESH:D005207), visceral adiposity (MESH:D007418), Obesity (MESH:D009765), impaired gut structure (MESH:D020914), Acute Malnutrition (MESH:D000067011), Gestational diabetes (MESH:D016640), weight gain (MESH:D015430), Hepatic steatosis (MESH:D005234), non-communicable disease (MESH:D000073296), Energy (MESH:D011502), overweight (MESH:D050177), Over (MESH:D006963), cardiomyopathy (MESH:D009202), wasting (MESH:D019282), sick euthyroid syndrome (MESH:D005067), Immune Dysfunction (MESH:D007154), infection (MESH:D007239), cardiovascular diseases (MESH:D002318), Protein deficiency (MESH:D011488), hepatic insulin resistance (MESH:D007333), child malnutrition (MESH:D015362), weight loss (MESH:D015431), endotoxemia (MESH:D019446), drought (MESH:C536747), anemia (MESH:D000740), long-term (MESH:D000088562), atherosclerosis (MESH:D050197), deaths (MESH:D003643), hyperinsulinemia (MESH:D006946), Malnutrition (MESH:D044342), Micronutrient deficiencies (MESH:D007153)
- **Chemicals:** cortisol (MESH:D006854), cortisone (MESH:D003348), Tricarboxylic Acid (MESH:D014233), Rapamycin (MESH:D020123), fat (MESH:D005223), zinc (MESH:D015032), nitric oxide (MESH:D009569), water (MESH:D014867), Vitamin A (MESH:D014801), amino acid (MESH:D000596), homocysteine (MESH:D006710), butyrate (MESH:D002087), carbohydrate (MESH:D002241), fatty acids (MESH:D005227), propionate (MESH:D011422), bile acid (MESH:D001647), 16-carbon monounsaturated fatty acids (-), T4 (MESH:D013974), T3 (MESH:D014284), LPC (MESH:D008244), acetate (MESH:D000085), Vitamin B6 (MESH:D025101), folate (MESH:D005492), SCFA (MESH:D005232), magnesium (MESH:D008274), pteridines (MESH:D011621), glucose (MESH:D005947), iodine (MESH:D007455), lipid (MESH:D008055), LPS (MESH:D008070)
- **Species:** Mus musculus (house mouse, species) [taxon 10090], Prevotella (genus) [taxon 838], Lactobacillus (genus) [taxon 1578], Escherichia coli (E. coli, species) [taxon 562], Veillonella (genus) [taxon 29465], Bacteroides (genus) [taxon 816], Staphylococcus aureus (species) [taxon 1280], Rattus norvegicus (brown rat, species) [taxon 10116], Homo sapiens (human, species) [taxon 9606], Streptococcus (genus) [taxon 1301], Bacteroidia (class) [taxon 200643], gut metagenome (species) [taxon 749906], Bacillota (clostridial firmicutes, phylum) [taxon 1239], Shigella (genus) [taxon 620]

## Full text

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## Figures

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## References

46 references — full list in the complete paper: https://tomesphere.com/paper/PMC12953344/full.md

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Source: https://tomesphere.com/paper/PMC12953344