Supplementary Material for: Visceral, not abdominal subcutaneous, fat cell size associates with metabolic dysfunction-associated liver disease in severe obesity

Introduction: Adipocyte hypertrophy is an important marker of adipose tissue dysfunction which significantly correlates with cardiometabolic risk factors. Fat cell size increases with adiposity and then plateaus at body mass index (BMI) values higher than 30 kg/m2. It is unknown whether fat cell size still associates with markers of dysmetabolism in severe obesity. Our objectives were to examine the associations between adipocyte diameter and markers of cardiometabolic health in a large sample of participants with severe obesity while adjusting for age, BMI and waist circumference. Methods: Biopsy samples of liver as well as abdominal subcutaneous and omental adipose tissues were obtained from 337 bariatric surgery patients. Evaluation of histological liver characteristics (steatosis, steatohepatitis, portal and lobular inflammation, hepatocellular ballooning and hepatic fibrosis) was performed by specialized pathologists. Adipocyte diameters were measured automatically using microscopy imaging. Lipid-lipoprotein profile, glucose-insulin homeostasis and adipokine levels were measured from blood samples. Results: Omental fat cell size was significantly larger with the presence of metabolic dysfunction-associated steatotic liver disease, metabolic dysfunction-associated steatohepatitis, liver fibrosis and lobular inflammation, as well as the presence and severity of portal inflammation. When stratified by gender, omental adipocytes were larger in women with liver injury, but not in men. Conclusion: In participants with severe obesity, associations between adipocyte hypertrophy and cardiometabolic risk factors are mostly seen in the omental fat compartment, and especially in women.