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Biomedicines
Volume 14
Issue 5
10.3390/biomedicines14051161
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Review

From Metabolically Healthy to Unhealthy Obesity Through Low-Grade Inflammation

by
Anastasia Voznesenskaya
†,
Alyona Sorokina
†,
Marina Shestakova
,
Ekaterina Shestakova
,
Ildar Minniakhmetov
,
Anna Ivanova
,
Sergey Rumyantsev
,
Natalia Mokrysheva
,
Vladimir Chekhonin
and
Marina Loguinova
*
Endocrinology Research Centre, 117292 Moscow, Russia
*
Author to whom correspondence should be addressed.
†
These authors contributed equally to this work.
Biomedicines 2026, 14(5), 1161; https://doi.org/10.3390/biomedicines14051161
Submission received: 10 March 2026 / Revised: 14 May 2026 / Accepted: 15 May 2026 / Published: 20 May 2026
(This article belongs to the Special Issue Obesity and Obesity-Related Pathology)
Review Reports Versions Notes

Abstract

Of the many clinical phenotypes of obesity, the most prevalent are metabolically “healthy” (MHO) and metabolically “unhealthy” (MUO) obesities, the latter being associated with a range of comorbidities, including type 2 diabetes mellitus (T2DM). The underlying causes of different obesity phenotypes and the mechanisms of conversion of one phenotype into another have yet to be fully elucidated. However, increasing evidence suggests the key role of low-grade metabolic inflammation (metaflammation) in the pathogenesis of obesity and metabolic dysfunction. The review presents a comprehensive description of changes in immune cell populations and pro-inflammatory mediators, as well as a detailed comparative mapping of the adipose tissue immune landscape during MHO/MUO transition. Based upon a conceptual model for the intensification of metaflammation during MHO progression and conversion to MUO, a pattern of dynamical changes that accompany MHO/MUO transition is described. Though many parameters demonstrate significant differences in multiple cross-sectional and some longitudinal studies, only a few of them (CRP, IL-6, IL-17A, absolute counts of leukocytes and neutrophils) meet the criteria of a validated biomarker in clinical setting. A lack of standardization in MHO definition and heterogeneity in the severity of MUO make the search for predictive biomarkers a challenge. The review also discusses the mechanisms underlying metabolic memory and the incomplete reversibility of metabolic disturbances after bariatric surgery.
Keywords: morbid obesity; type 2 diabetes mellitus (T2DM); metaflammation, bariatric surgery; obesogenic memory; CRP; IL-6; IL-17A; senescent immune cells morbid obesity; type 2 diabetes mellitus (T2DM); metaflammation, bariatric surgery; obesogenic memory; CRP; IL-6; IL-17A; senescent immune cells

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MDPI and ACS Style

Voznesenskaya, A.; Sorokina, A.; Shestakova, M.; Shestakova, E.; Minniakhmetov, I.; Ivanova, A.; Rumyantsev, S.; Mokrysheva, N.; Chekhonin, V.; Loguinova, M. From Metabolically Healthy to Unhealthy Obesity Through Low-Grade Inflammation. Biomedicines 2026, 14, 1161. https://doi.org/10.3390/biomedicines14051161

AMA Style

Voznesenskaya A, Sorokina A, Shestakova M, Shestakova E, Minniakhmetov I, Ivanova A, Rumyantsev S, Mokrysheva N, Chekhonin V, Loguinova M. From Metabolically Healthy to Unhealthy Obesity Through Low-Grade Inflammation. Biomedicines. 2026; 14(5):1161. https://doi.org/10.3390/biomedicines14051161

Chicago/Turabian Style

Voznesenskaya, Anastasia, Alyona Sorokina, Marina Shestakova, Ekaterina Shestakova, Ildar Minniakhmetov, Anna Ivanova, Sergey Rumyantsev, Natalia Mokrysheva, Vladimir Chekhonin, and Marina Loguinova. 2026. "From Metabolically Healthy to Unhealthy Obesity Through Low-Grade Inflammation" Biomedicines 14, no. 5: 1161. https://doi.org/10.3390/biomedicines14051161

APA Style

Voznesenskaya, A., Sorokina, A., Shestakova, M., Shestakova, E., Minniakhmetov, I., Ivanova, A., Rumyantsev, S., Mokrysheva, N., Chekhonin, V., & Loguinova, M. (2026). From Metabolically Healthy to Unhealthy Obesity Through Low-Grade Inflammation. Biomedicines, 14(5), 1161. https://doi.org/10.3390/biomedicines14051161

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