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Peer-reviewedCC BYMetabolism Open

The normal-weight metabolic syndrome: Clinical manifestations and pathogenic mechanisms

  • John Nzobokela1
  • Bisom Chikwanka Mweene2
  • Elletina Nchimunya Sinamwenda3
  • Situmbeko Liweleya4
  • Sepiso K. Masenga
  • Lweendo Muchaili5
  • Benson M. Hamooya6
6 affiliations
  1. 1Department of Cardiovascular Science and Metabolic Diseases, Livingstone Center for Prevention and Translational Sciences, Livingstone, Zambia; Corresponding author.
  2. 2Department of Cardiovascular Science and Metabolic Diseases, Livingstone Center for Prevention and Translational Sciences, Livingstone, Zambia; Pathology and Microbiology Department, School of Medicine and Health Sciences, Mulungushi University, Livingstone, Zambia
  3. 3Nursing Department, School of Nursing and Midwifery, Mulungushi University, Kabwe, Zambia
  4. 4Pathology and Microbiology Department, School of Medicine and Health Sciences, Mulungushi University, Livingstone, Zambia
  5. 5Department of Cardiovascular Science and Metabolic Diseases, Livingstone Center for Prevention and Translational Sciences, Livingstone, Zambia; Nursing Department, School of Nursing and Midwifery, Mulungushi University, Kabwe, Zambia; Pathology and Microbiology Department, School of Medicine and Health Sciences, Mulungushi University, Livingstone, Zambia
  6. 6Department of Cardiovascular Science and Metabolic Diseases, Livingstone Center for Prevention and Translational Sciences, Livingstone, Zambia; Department of Public Health, School of Medicine and Health Sciences, Mulungushi University, Livingstone, Zambia
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Abstract

Metabolic syndrome (MetS), conventionally associated with obesity, also occurs in individuals with a normal body mass index (BMI), revealing an important discordance between body weight and metabolic health. This phenotype, variably described as normal-weight metabolic syndrome (NWMS), metabolically obese normal weight (MONW), or metabolically unhealthy normal weight (MUNW), is characterized by metabolic abnormalities despite the absence of generalized obesity. Reported prevalence varies substantially across populations because of heterogeneity in phenotype definitions, BMI thresholds, metabolic criteria, and population characteristics, and the global burden remains uncertain. Nevertheless, affected individuals have an increased risk of type 2 diabetes and cardiovascular disease compared with metabolically healthy normal-weight individuals. This review critically synthesizes current evidence on the epidemiology, clinical manifestations, diagnostic approaches, and pathogenic mechanisms of NWMS. Visceral and ectopic adiposity, insulin resistance, adipose tissue dysfunction, and chronic low-grade inflammation represent the most consistently supported pathogenic pathways. In contrast, gut microbiota dysbiosis, oxidative stress, ferroptosis, and related molecular processes remain emerging mechanisms with limited evidence specific to normal-weight populations. Recognition of metabolic risk beyond BMI is therefore important, particularly in susceptible populations. A risk-based approach incorporating conventional metabolic assessment, measures of central adiposity, and selective body-composition assessment may improve identification of affected individuals. Harmonized phenotype definitions and studies across geographically and ethnically diverse populations are needed to define the global burden and inform targeted prevention and management strategies.

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Cite

BibTeXRIS
BibTeX
@article{nzobokela2026normalweight,
  title = {{The normal-weight metabolic syndrome: Clinical manifestations and pathogenic mechanisms}},
  author = {John Nzobokela and Bisom Chikwanka Mweene and Elletina Nchimunya Sinamwenda and Situmbeko Liweleya and Sepiso K. Masenga and Lweendo Muchaili and Benson M. Hamooya},
  journal = {Metabolism Open},
  year = {2026},
  month = oct,
  doi = {10.1016/j.metop.2026.100513},
  url = {https://doi.org/10.1016/j.metop.2026.100513},
  note = {CC BY},
}
RIS
TY  - JOUR
TI  - The normal-weight metabolic syndrome: Clinical manifestations and pathogenic mechanisms
AU  - John Nzobokela
AU  - Bisom Chikwanka Mweene
AU  - Elletina Nchimunya Sinamwenda
AU  - Situmbeko Liweleya
AU  - Sepiso K. Masenga
AU  - Lweendo Muchaili
AU  - Benson M. Hamooya
PY  - 2026
DA  - 2026/10/31
JO  - Metabolism Open
DO  - 10.1016/j.metop.2026.100513
UR  - https://doi.org/10.1016/j.metop.2026.100513
AB  - Metabolic syndrome (MetS), conventionally associated with obesity, also occurs in individuals with a normal body mass index (BMI), revealing an important discordance between body weight and metabolic health. This phenotype, variably described as normal-weight metabolic syndrome (NWMS), metabolically obese normal weight (MONW), or metabolically unhealthy normal weight (MUNW), is characterized by metabolic abnormalities despite the absence of generalized obesity. Reported prevalence varies substantially across populations because of heterogeneity in phenotype definitions, BMI thresholds, metabolic criteria, and population characteristics, and the global burden remains uncertain. Nevertheless, affected individuals have an increased risk of type 2 diabetes and cardiovascular disease compared with metabolically healthy normal-weight individuals. This review critically synthesizes current evidence on the epidemiology, clinical manifestations, diagnostic approaches, and pathogenic mechanisms of NWMS. Visceral and ectopic adiposity, insulin resistance, adipose tissue dysfunction, and chronic low-grade inflammation represent the most consistently supported pathogenic pathways. In contrast, gut microbiota dysbiosis, oxidative stress, ferroptosis, and related molecular processes remain emerging mechanisms with limited evidence specific to normal-weight populations. Recognition of metabolic risk beyond BMI is therefore important, particularly in susceptible populations. A risk-based approach incorporating conventional metabolic assessment, measures of central adiposity, and selective body-composition assessment may improve identification of affected individuals. Harmonized phenotype definitions and studies across geographically and ethnically diverse populations are needed to define the global burden and inform targeted prevention and management strategies.
SN  - 2589-9368
ER  -