Divergent ectopic fat distribution and adipokine/hepatokine levels characterize the metabolically healthy overweight/obesity phenotype

The metabolically healthy overweight/obesity (MHOO) phenotype combines excess adiposity with preserved cardiometabolic health. We compared specific fat depots, circulating adipokine and hepatokine levels, and fecal microbiota composition between 384 adults classified as MHOO ( n = 99) or metabolically unhealthy overweight/obesity (MUOO; n = 285). Magnetic resonance imaging was used to quantify visceral adipose tissue (VAT) volume, hepatic and pancreatic fat fractions, abdominal and mid-thigh intermuscular adipose tissue (IMAT), and subcutaneous adipose tissue (SAT). Despite similar whole-body fat mass, MHOO showed lower VAT volume, hepatic and pancreatic fat fractions, abdominal IMAT volume, abdominal VAT-to-SAT ratio, and mid-thigh IMAT area, together with higher mid-thigh SAT area. MHOO also had higher adiponectin and sex hormone-binding globulin (SHBG) and lower retinol-binding protein 4 (RBP4) levels. Fecal microbiota composition was similar between groups. VAT volume and hepatic fat fraction were the strongest discriminative features, supporting fat distribution rather than total adiposity as a key feature of preserved metabolic health.