Energy Metabolism in Human Obesity

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Abstract
The lipid-mobilizing action of epinephrine was compared in obese and control subjects in 2 separate experiments: an initial study in which plasma free fatty acid (FFA) and glucose levels were determined before and 30 minutes after the subcutaneous injection of 0.5 mg aqueous epinephrine and a subsequent study, incorporating plasma glycerol measurements, in which the test period was extended to 2 hours. Overall results revealed that 11 of 59 obese patients tested (19%) failed to respond to epinephrine with any significant rise in plasma FFA and an additional 9 patients showed a delayed fall-off in FFA after peak response was reached. A disparity between changes in plasma FFA and glycerol measurements was in the latter subjects, resulting in abnormally high FFA/glycerol molar ratios. A significant correlation existed between obese individuals displaying epinephrine resistance and abnormalities in peripheral glucose and oxidative metabolism. A marked lowering of basal FFA levels and normal responsiveness to epinephrine was achieved in these obese subjects following treatment with L-triiodothyronine; concomitant improvement in glucose tolerance and glucose oxidation to CO2 was also noted. It remains undetermined whether the abnormalities in FFA dynamics delineated in certain obese subjects during prolonged fasting or after epinephrine stimulation are due to enzymatic defects in the mobilization and utilization of FFA or stem from basic derangements in the glucose-FFA cycle in adipose tissue. Similar abnormalities in FFA metabolism was noted in congenitally obese hyperglycemic mice and are believed to play an important role in the metabolic form of obesity in both humans and animals.

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