Adiposology: A Tissue-centric Clinical Framework for Cardiometabolic Risk Beyond Body Mass Index

Abstract Adiposology conceptualizes obesity primarily as a disorder of adipose tissue function rather than body size, with adipose tissue dysfunction expressed across four clinically relevant domains: fat distribution, limited expandability with fibrosis, altered immune–endocrine signaling, and ectopic lipid deposition. This perspective explains the cardiometabolic risk heterogeneity that remains unaccounted for by body mass index (BMI) alone. In this narrative, concept-driven review, mechanistic and clinically relevant human evidence from PubMed and Scopus (2005–2024), supplemented by targeted Consensus AI searches, was synthesized to inform a unifying clinical framework. We propose a clinician-oriented framework that integrates practical clinical proxies, such as waist-to-height ratio, triglyceride-to-high-density lipoprotein cholesterol ratio, alanine aminotransferase or fatty liver index, glycated hemoglobin A1c, and surrogate markers of insulin resistance, within a stepwise pathway for screening, phenotyping, and risk prioritization. A complementary, mechanism-based intervention map is outlined to link these phenotypes with strategies aimed at reducing visceral and ectopic lipid burden, preserving cardiorenal function, and improving insulin sensitivity. This tissue-centric model supports phenotype-based clinical decision-making. It also enables electronic health record–embedded risk scoring with prospective validation aligned with the Transparent Reporting of a multivariable prediction model for Individual Prognosis Or Diagnosis (TRIPOD) principles. It improves applicability across age, sex, and ethnic groups, including populations with higher cardiometabolic risk at lower BMI thresholds.