Physiological Mechanisms of Weight Gain-Induced Steatosis in People With Obesity

Abstract

Weight gain is associated with an increase in intrahepatic triglycerides (IHTGs), and is the primary cause of nonalcoholic fatty liver disease in obese individuals. We combined imaging and stable isotope tracer techniques to evaluate the physiologic mechanisms of weight gain-induced steatosis in 27 obese people. Weight gain appeared to increase IHTG content by generating an imbalance between hepatic fatty acid availability and disposal, and resulted in increased hepatic de novo lipogenesis, decreased intrahepatic fatty acid oxidation, and inadequate increases in IHTG export via very low-density lipoprotein secretion. ClinicalTrials.gov ID NCT01184170.

Keywords: Fatty Acid Oxidation; Overweight; VLDL; apoB100.

Figure 1

Effect of moderate weight gain on: A) hepatic de novo lipogenesis, assessed as fatty acid produced from carbohydrate precursors and incorporated into very low-density lipoprotein-triglyceride (VLDL-TG); B) β-hydroxybutyrate rate of appearance (Ra); C) hepatic secretion of VLDL-apolipoprotein B100 (VLDL-apoB100); and D) hepatic secretion of VLDL- TG, and contribution of systemic (dark grey) and non-systemic (light grey) fatty acid sources to triglyceride secreted within VLDL. *Value different from before weight gain value, P<0.05. Data are back-transformed from the log and are presented as means and 95% CIs.