CHANGES IN GLUCOSE AND LIPID-METABOLISM FOLLOWING WEIGHT-LOSS PRODUCED BY A VERY-LOW-CALORIE DIET IN OBESE SUBJECTS

OBJECTIVE: To study the effects of a very low calorie diet (VLCD) on g lucose and lipid metabolism in obese subjects, in particular, the effe cts on insulin sensitivity and the activities of the key enzymes of gl ucose disposal, glycogen synthase (GS) and the pyruvate dehydrogenase complex (PDHC). DESIGN: Clinical dietary intervention study (1.67 MJ ( 400 kcal)/day) until weight loss of >10%. SUBJECTS: 11 (seven male, fo ur female) non-diabetic, obese subjects (age:27-62 y; BMI:40.5 +/- 1.4 kg/m(2)). MEASUREMENTS: Whole body glucose disposal (by euglycemic hy perinsulinemic clamp), respiratory quotient (RO), resting energy expen diture (REE), glucose and lipid oxidation (by indirect calorimetry), i nsulin-stimulated PDHC and GS activity (in muscle biopsies) both befor e and immediately after VLCD (i.e. while still in a hypocaloric state) , serum hormone and metabolite levels throughout the dietary period. R ESULTS: Weight loss was accompanied by reduced insulin and elevated NE FA levels, improved insulin sensitivity due to increased nonoxidative glycolysis with no increase in PDHC or GS activities, The rate of weig ht loss was inversely related to the initial RO. PDHCa was strongly ag e-related. CONCLUSION: A low RQ may be used as a predictor of the effi cacy of VLCD treatment and that while VLCD improves nonoxidative glyco lytic flux, changes in oxidative glucose disposal and muscle glucose s torage are prevented by high NEFA availability during this catabolic p hase of dietary intervention.