1866-P: Adipocyte Hypertrophy Is Associated with Increased Dietary Fatty Acid Storage in Adipose Tissue and Reduced Postprandial Hepatic Fatty Acid Uptake and Esterification in Humans

Introduction: Excessive exposure of lean tissues to nonesterified fatty acids (NEFA) leads to insulin resistance (IR). Adipocyte hypertrophy is associated with IR and increase in adipose tissue intracellular triglyceride lipolysis and in NEFA levels, that may contribute to hepatic steatosis and IR. The effect of adipocyte hypertrophy on postprandial hepatic NEFA flux and metabolism and dietary fatty acids (DFA) storage in adipose tissues has not been studied, however. Methods: In 28 healthy adult subjects, fat cell size (FCS) was determined via histomorphologic analysis of abdominal subcutaneous fat tissue. Adipose tissue DFA storage was measured using oral administration of 18FTHA with positron emission tomography (PET). Postprandial hepatic NEFA uptake, oxidation, and esterification were determined using intravenous 11C-palmitate with dynamic PET acquisition. Results: As expected, FCS was correlated positively with fasting glycemia (ρ=0.44, P-value=0.029), homeostasis model assessment-estimated insulin resistance (HOMA-IR) (ρ=0.43, P-value=0.049), and hepatic fat content from CT radiodensity (ρ=0.32, P-value=0.10). FCS was correlated positively with DFA storage in intra-abdominal adipose tissues (ρ=0.48, P-value=0.022) and negatively with postprandial hepatic NEFA uptake (ρ=-0.42, P-value=0.027) and esterification (ρ=-0.58, P-value=0.0080). Conclusion: Adipocyte hypertrophy is associated with increased DFA storage in intra-abdominal adipose tissues and reduced postprandial hepatic NEFA uptake and esterification, despite being associated with greater hepatic fat content, fasting glycemia and HOMA-IR. Adipocyte hypertrophy is thus associated with adipose tissue metabolic adaptation that limits the exposure of the liver to fatty acids in the postprandial period.