The effects of short-term overfeeding on adipocyte metabolism in pima Indians

Abstract

The effects on adipocyte metabolism of increasing daily caloric intake by approximately 60% for 14 days was studied in seven nondiabetic moderately obese southwestern Native American Indians. Mean body weight increased by 3.0 ± 0.3 kg, without any change in average size of isolated abdominal adipocytes. Overfeeding resulted in a 58% increase ( P < 0.01) in mean fasting plasma insulin concentration, whereas fasting plasma glucose concentration remained constant. Basal and maximum (8 nmol/L) insulin-stimulated glucose transport rates by isolated adipocytes increased by 83% ( P < 0.02) and 110% ( P < 0.01), respectively, after overfeeding, associated with an increase of 118% ( P < 0.01) in the incremental response to maximal insulin stimulation. However, no differences in either the sensitivity (ED 50 of insulin for the stimulation of glucose transport) or the responsiveness (percent stimulation by insulin) of glucose transport were seen in isolated adipocytes as a result of overfeeding. Maximum insulin-stimulated total glucose utilization rates by isolated adipocytes incubated at 5.5 mmol/L glucose were 63% greater after overfeeding, due to increases in lactate formation, triglyceride synthesis, and CO 2 production. Mono 125I-(Tyr A 14)-insulin binding per cell and per cell surface area was similar before and after overfeeding. The lipolytic rate of isolated adipocytes, in the absence and presence of 25 nmol/L and 2 μmol/L isoproterenol, was decreased by 75% ( P < 0.02), 45% ( P < 0.05), and 27% ( P < 0.05), respectively, after overfeeding. However, overfeeding did not result in a significant difference in the sensitivity of antilipolysis to insulin. These results suggest that the short-term ingestion of a hypercaloric diet leads to profound changes in basal and insulin-stimulated glucose transport, glucose metabolism and lipolysis by isolated adipocytes. These effects occurred in association with hyperinsulinemia, which did not produce down-regulation of insulin binding. Since changes in dietary composition were not introduced, it is tempting to speculate that the effects on adipocyte metabolism were due to the hyperinsulinemia induced by the overfeeding.