Lipolysis and gluconeogenesis from glycerol during weight reduction with very-low-calorie diets

Abstract

The aim of this study was to determine if the rates of lipolysis and the conversion of glycerol into glucose are higher during weight reduction with a ketogenic than a nonketogenic very-low-calorie diet (VLCD). Sixteen obese women were randomly assigned to consume either a ketogenic or nonketogenic 615-kcal/d diet for 28 days while confined to a metabolic ward. Glycerol and glucose rates of appearance (R_as) and the conversion of glycerol into glucose were measured before and after 14 and 28 days of treatment with a simultaneous, primed, constant infusion of U-[¹⁴C]-glycerol and 6-[³H]-glucose. Resting energy expenditure (REE) and rates of substrate oxidation were measured by indirect calorimetry. Data were analyzed by repeated-measures ANOVA. There were no diet or time effects on the plasma glycerol concentration or glycerol R_a. There was a modest but significant time effect on the glucose R_a and on the conversion of glycerol into glucose when expressed as a percentage of the glycerol or glucose R_a. However, even after 28 days of treatment, the conversion of glycerol into glucose accounted for only 16% and 58% of glucose and glycerol R_as, respectively. At day 28, plasma glucose and alanine concentrations were lower and the rate of protein oxidation was higher in the ketogenic than in the nonketogenic VLCD group. We conclude that in severe obesity, (1) the rates of lipolysis and gluconeogenesis from glycerol are not increased by altering the composition of the VLCD; (2) glycerol is a minor gluconeogenic precursor during weight reduction; and (3) nonketogenic VLCDs are more advantageous than ketogenic VLCDs in maintaining normal plasma glucose concentration and promoting protein sparing.