Metabolically healthy obesity as a latent health risk

UDC: 
616-092.12
DOI: 
10.21668/health.risk/2026.1.12.eng
Authors: 

S.I. Kseneva1, O.Y. Trifonova1, E.A. Pykhtunova1, A.A. Zolotarev1, V.V. Udut1,2

Organization: 

1Goldberg Research Institute of Pharmacology and Regenerative Medicine of Tomsk National Research Medical Centre of the Russian Academy of Sciences, 3 Lenina Ave., Tomsk, 634028, Russian Federation
2National Research Tomsk State University, 36 Lenina Ave., Tomsk, 634050, Russian Federation

Abstract: 

The phenomenon of ‘metabolically healthy obesity’ is of great interest to researchers around the world. This is determined by two complementary standpoints: 1) the investigated obesity phenotype, under exposure to additional risk factors, may represent an intermediate state leading to ‘metabolic unhealthiness’; and 2) if this is true, this phenotype is a research object for searching triggers of diseases prevention. Due to absence of biochemically substantiated changes, groups of analyzed pre-nosologic states were divided per body mass index as an integral sign of metabolism effectiveness. This was made allowing for the obviously multi-level structure of metabolic processes where the physiological optimum as the main target is maintained at the cellular level and compensation for growing deviations requires involvement of the managing nuerohumoral system, vegetative regulation included. This is manifested through changes in structures that support metabolic homeostasis.
The aim of this study was to estimate the reserve and stability of regulatory metabolic systems within analyzing potential cardiometabolic risks for people with ‘metabolically healthy obesity’.

A single-time cross-sectional study was conducted on a continuous sample of 34 healthy volunteers aged 18 to 43 years with body mass index of 18.5 to 30.0 kg/m2 and a verified diagnosis of ‘healthy’. Using standard laboratory methods, biochemical blood tests were performed one hour after a standardized meal, and insulin and cortisol levels were additionally determined in blood plasma.

Standardized food load was used as a universal irritant in estimating changes in the metabolic status as a health measure. This allowed us to reveal the maximum involvement of metabolic regulators or the system ‘tension’.

We analyzed strength of statistical relationships between analyzed indicators. The analysis clearly showed that ‘higher’ levels of metabolic regulations steadily became more and more involved in healthy volunteers as their body weight grew and hyperinsulinemia occurred. This involvement grew from the first cellular level that induced a strictly identified specific response aimed at achieving a justified physiological effect and determined point control through the organ level where local interactions became more tensed to the body level where physiological responses occurred with their orientation at long-term effects.

When control over metabolism regulation goes to the nuerohumoral system in hyperinsulinemia presence, this means a certain functional mark in evolution of ‘metabolically healthy obesity’. This process is the key link in an individual risk trajectory since it marks the transition from compensated pseudo-health to a phase when prenosologic disorders are formed quite actively. Personalized risk stratification and timely preventive interventions should rely on revealing and estimating this process.

Keywords: 
metabolically healthy obesity, metabolism regulation, metabolic syndrome, diabetes mellitus, metabolic phenotype, hormones, insulin, cortisol
Kseneva S.I., Trifonova O.Yu., Pykhtunova E.A., Zolotarev A.A., Udut V.V. Metabolically healthy obesity as a latent health risk. Health Risk Analysis, 2026, no. 1, pp. 125–133. DOI: 10.21668/health.risk/2026.1.12.eng
References: 
  1. Blüher M. Metabolically healthy obesity. Endocr. Rev., 2020, vol. 41, no. 3, pp. bnaa004. DOI: 10.1210/endrev/bnaa004
  2. Gómez-Zorita S., Queralt M., Vicente M.A., González M., Portillo M.P. Metabolically healthy obesity and metabolically obese normal weight: a review. J. Physiol. Biochem., 2021, vol. 77, no. 1, pp. 175–189. DOI: 10.1007/s13105-020-00781-x
  3. April-Sanders A.K., Rodriguez C.J. Metabolically Healthy Obesity Redefined. JAMA Netw. Open, 2021, vol. 4, no. 5, pp. e218860. DOI: 10.1001/jamanetworkopen.2021.8860
  4. Soriguer F., Gutiérrez-Repiso C., Rubio-Martín E., García-Fuentes E., Almaraz M.C., Colomo N., de Antonio I.E., de Adana M.S.R. [et al.]. Metabolically healthy but obese, a matter of time? Findings from the prospective Pizarra study. J. Clin. Endocrinol. Metab., 2013, vol. 98, no. 6, pp. 2318–2325. DOI: 10.1210/jc.2012-4253
  5. Boyarinova M.A., Rotar O.P., Erina A.M., Paskar N.A., Alieva A.S., Moguchaia E.V., Kolesova E.P., Konradi A.O. Metabolically healthy obesity: predictors of transformation to unhealthy phenotype in St Petersburg population (according to the ESSE-RF study). Arterial’naya gipertenziya, 2021, vol. 27, no. 3, pp. 279–290. DOI: 10.18705/1607-419X-2021-27-3-279-290 (in Russian).
  6. Barrea L., Muscogiuri G., Pugliese G., de Alteriis G., Colao A., Savastano S. Metabolically Healthy Obesity (MHO) vs. Metabolically Unhealthy Obesity (MUO) Phenotypes in PCOS: Association with Endocrine-Metabolic Profile, Adherence to the Mediterranean Diet, and Body Composition. Nutrients, 2021, vol. 13, no. 11, pp. 3925. DOI: 10.3390/nu13113925
  7. Imai J., Katagiri H. Regulation of systemic metabolism by the autonomic nervous system consisting of afferent and efferent innervation. International Immunology, 2022, vol. 34, no. 2, pp. 67–79. DOI: 10.1093/intimm/dxab023
  8. Ametov A.S. Insulin secretion and insulin resistance: two sides of one medal. Problemy endokrinologii, 2002, vol. 48, no. 3, pp. 31–37. DOI: 10.14341/probl11613 (in Russian).
  9. Klimontov V.V., Saik O.V., Korbut A.I. Glucose Variability: How Does It Work? Int. J. Mol. Sci., 2021, vol. 22, no. 15, pp. 7783. DOI: 10.3390/ijms22157783
  10. Holst J.J., Gasbjerg L.S., Rosenkilde M.M. The Role of Incretins on Insulin Function and Glucose Homeostasis. Endo-crinology, 2021, vol. 162, no. 7, pp. bqab065. DOI: 10.1210/endocr/bqab065
  11. Billman G.E. Homeostasis: The underappreciated and far too often ignored central organizing principle of physiology. Front. Physiol., 2020, vol. 11, pp. 200. DOI: 10.3389/fphys.2020.00200
  12. Adasheva T.V., Demicheva O.Yu. Metabolicheskii sindrom – osnovy patogeneticheskoi terapii [Metabolic syndrome – the basis of pathogenetic therapy]. Lechashchii vrach, 2003, no. 10, pp. 24–28 (in Russian).
  13. Hall K.D., Farooqi I.S., Friedman J.M., Klein S., Loos R.J.F., Mangelsdorf D.J., O'Rahilly S., Ravussin E. [et al.]. The energy balance model of obesity: beyond calories in, calories out. Am. J. Clin. Nutr., 2022, vol. 115, no. 5, pp. 1243–1254. DOI: 10.1093/ajcn/nqac031
  14. Dimitriadis G.D., Maratou E., Kountouri A., Board M., Lambadiari V. Regulation of Postabsorptive and Postprandial Glucose Metabolism by Insulin-Dependent and Insulin-Independent Mechanisms: An Integrative Approach. Nutrients, 2021, vol. 13, no. 1, pp. 159. DOI: 10.3390/nu13010159
  15. Alghannam A.F., Ghaith M.M., Alhussain M.H. Regulation of energy substrate metabolism in endurance exercise Int. J. Environ. Res. Public Health, 2021, vol. 18, no. 9, pp. 4963. DOI: 10.3390/ijerph18094963
  16. Grabner G.F., Xie H., Schweiger M., Zechner R. Lipolysis: cellular mechanisms for lipid mobilization from fat stores. Nat. Metab., 2021, vol. 3, no. 11, pp. 1445–1465. DOI: 10.1038/s42255-021-00493-6
  17. Wang Y., Yu W., Li S., Guo D., He J., Wang Y. Acetyl-CoA Carboxylases and Diseases. Front. Oncol., 2022, vol. 12, pp. 836058. DOI: 10.3389/fonc.2022.836058
  18. Tkachuk V.A., Vorotnikov A.V. Molecular Mechanisms of Insulin Resistance Development. Sakharnyi diabet, vol. 17, no. 2, pp. 29–40. DOI: 10.14341/DM2014229-40 (in Russian).
  19. Wilson D.F., Matschinsky F.M. Metabolic homeostasis in life as we know it: Its origin and thermodynamic basis. Front. Physiol., 2021, vol. 12, pp. 658997. DOI: 10.3389/fphys.2021.658997
Received: 
14.11.2025
Approved: 
11.03.2026
Accepted for publication: 
26.03.2026

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