J Basic Clin Physiol Pharmacol. 2026 Oct 23. doi: 10.1515/jbcpp-2026-0266. Online ahead of print.
ABSTRACT
Metabolically healthy obesity (MHO) is a heterogeneous phenotype characterized by preserved traditional metabolic markers despite excess adiposity. However, accumulating evidence suggests that MHO may not be uniformly benign and may confer increased long-term cardiovascular risk through inflammatory and adipose tissue-mediated mechanisms. This narrative review synthesizes contemporary evidence on cardiovascular risk in MHO, focusing on visceral adiposity, ectopic fat, and immune metabolic pathways. Literature published between January 2010 and December 2025 was identified through PubMed/MEDLINE, Embase, Web of Science, and Cochrane Library. Across the reviewed evidence, MHO is frequently associated with the progression to metabolically unhealthy obesity, although transition rates and cardiovascular risk estimates vary according to MHO definitions. Visceral and ectopic fat are associated with subclinical atherosclerosis, coronary calcification, and cardiovascular events, including in individuals without overt metabolic abnormalities. Evidence regarding heart failure and ventricular dysfunction remains limited and inconsistent. Low-grade inflammation and adipose immune remodeling, including NLRP3 inflammasome activation, provide plausible mechanisms, although human evidence remains predominantly observational. Key gaps include inconsistent MHO definitions, limited longitudinal imaging and biomarker integration, population diversity, and lack of validated MHO-specific risk models. Standardized phenotyping and prospective validation of inflammation-based risk stratification are required.
PMID:42912250 | DOI:10.1515/jbcpp-2026-0266