Substrate cycling between triglyceride and fatty acid in human adipocytes

Abstract

Substrate cycles in metabolism require energy and generate heat, and they may be involved in thermogenesis. We have studied one such cycle between triglyceride and fatty acid in isolated human adipocytes using a nonisotopic technique. In the absence of added hormone, and with 5 mmol/L (90 mg/dL) glucose in the incubation medium, lipolysis and fatty acid reesterification coexisted such that 40 ± 4% (mean ± SEM) of the fatty acid produced was cycled back into triglyceride. In 51 individual subjects the range was from 0% to 100%. Both lipolysis and the quantity of fatty acid recycled correlated positively with cell volume ( P < .001 and P < .005, respectively). Norepinephrine (10 −6 mol/L) alone (33 experiments) increased lipolysis 3.1-fold, and reduced the percentage of fatty acid reesterified. Cycling was similar to that in the basal state. Lipolysis was inhibited 46% by postabsorptive levels of insulin alone (18 experiments), but the proportion of fatty acid reesterified increased such that the quantity cycled back into triglyceride was similar to that observed in the basal state. In the presence of both norepinephrine and insulin (18 experiments), lipolysis was increased by 58% while 31 ± 4% of the fatty acid released was reesterified. In consequence, the quantity of fatty acid cycled back into triglyceride increased 2.1-fold. Increasing the insulin level fivefold or the medium glucose concentration to 20 mmol/L produced no further increase in the quantity of fatty acid reesterified. A substrate cycle exists, therefore, between triglyceride and fatty acid in human adipose tissue, and its activity is modified by norepinephrine and insulin. The predicted daily energy cost of this substrate cycle in 5 to 12 kcal (22 to 48 kJ) in lean subjects, and 10 to 20 kcal (41 to 82 kJ) in the obese.