Maladaptive lipid partitioning in obesity-related heart failure with preserved ejection fraction: From depot dysfunction to metabolic phenotyping

Table 1 Depot-specific adipose and organ pathways in obesity-related heart failure with preserved ejection fraction

Depot or organ axis	Representative evidence	Proposed mechanism	Clinical measurability	Evidence maturity/key limitation
Subcutaneous adipose tissue	Lower subcutaneous adiposity, together with lower visceral adiposity, was associated with underweight, malnutrition, and poorer outcomes in an East Asian HFpEF cohort[6]; impaired lipid-buffering remains primarily a conceptual framework[8]	Lipid spillover to ectopic depots	Body composition; indirect metabolic markers	Human observational association plus review-level conceptual evidence; direct subcutaneous lipid-buffering capacity has not been established in HFpEF (CT-based East Asian HFpEF cohort, n = 196 + contemporary review)
Visceral adiposity	Visceral or central adiposity is associated with exercise limitation, higher exercise filling pressures, and poorer aerobic capacity[5,22]	Insulin-resistant lipid stress; inflammatory activation	CT/MRI; waist indices; visceral adiposity measures	Human observational and invasive-physiology evidence; causality remains unproven (HFpEF imaging cohort + invasively phenotyped HFpEF cohort)
MASLD/liver	MASLD is associated with incident heart failure, including HFpEF, whereas experimental NASH produces an HFpEF-like phenotype[20,21]	Hepatic-metabolic stress; systemic inflammation	Liver fat/stiffness; liver enzymes; metabolic risk indices	Human longitudinal association plus preclinical mechanistic evidence; human causality remains uncertain (longitudinal human cohort + experimental NASH model)
Skeletal-muscle fat	Intermuscular fat is associated with worse functional limitation, and impaired skeletal muscle mitochondrial respiration is associated with exercise intolerance[22,28]	Impaired peripheral metabolic and oxygen-utilization reserve	CT/MRI muscle composition; grip strength; gait speed	Human imaging/biopsy associations; clinically validated thresholds are lacking (human HFpEF imaging + skeletal biopsy studies)
Epicardial adipose tissue	EAT burden is associated with pericardial constraint and atrial/ventricular dysfunction, whereas lower EAT density is associated with adverse cardiometabolic phenotype and outcomes[23,24,40]	Local mechanical and paracrine amplifier	Echocardiography, CT, CMR; EAT volume/density	Human observational, invasive-physiology, and prospective imaging evidence; EAT density is not a direct measure of inflammation and whether EAT is a mediator or marker remains unresolved (HFpEF observational/invasive-physiology cohorts + prospective imaging cohort, n = 154)
Perivascular adipose tissue	Pericoronary adipose tissue attenuation on CT is associated with HFpEF[41]	Possible vascular-adipose inflammatory and remodeling interface	CT perivascular fat attenuation	Retrospective human imaging association; direct causal and histological validation in HFpEF is lacking (retrospective CCTA/echocardiography cohort, n = 607)

HFpEF: Heart failure with preserved ejection fraction; CT: Computed tomography; MRI: Magnetic resonance imaging; MASLD: Metabolic dysfunction-associated steatotic liver disease; NASH: Non-alcoholic steatohepatitis; EAT: Epicardial adipose tissue; CMR: Cardiovascular magnetic resonance; CCTA: Coronary computed tomographic angiography.