EFFECTS OF LONG-TERM TOTAL FASTING AND INSULIN ON OB GENE-EXPRESSION IN OBESE PATIENTS

In the present study the effect of long-term fasting (6 days) on obese (ob) gene expression was examined in nine severely obese females of 3 4+/-3 years and with a body mass index of 46.4+/-2.3 kg/m(2). Six days of fasting induced a significant weight loss (126.8+/-5.3 vs 120.5+/- 5.1 kg. P<0.0001), Insulin-stimulated glucose uptake (hyperinsulinemic , euglycemic clamp, insulin infusion rate 1.5 mU/kg per min) was marke dly reduced following fasting (M-value 5.96+/-0.74 vs 2.79+/-0.23 mg/k g per min, P<0.0001), Ob mRNA/beta-actin concentration in fat biopsies from abdominal subcutaneous adipose tissue was unchanged after 6 days of fasting (1.50+/-0.40 vs 1.47+/-0.36 arbitrary units, not significa nt), whereas serum leptin levels decreased significantly from 53.8+/-4 .7 to 30.7+/-2.0 ng/ml (P<0.0001) during the same period. No significa nt correlations were found between insulin-stimulated glucose uptake a nd serum leptin concentration, either prior to the fast or after the f ast, Serum leptin levels were unchanged by hyperinsulinemia for 3 h du ring the clamp prior to the fast, while hyperinsulinemia for 3 h after 6 days of fasting increased serum leptin by 25% (P<0.01). In conclusi on, 6 days of fasting reduced serum leptin by about 40%, In contrast, ob mRNA, in abdominal subcutaneous adipose tissue was unchanged, Furth ermore, after 6 days of fasting insulin was able to increase the serum level of leptin significantly indicating that the effect of insulin o n the level of leptin is dependent on the nutritional state.