Objective: Leptin secretion has been shown to respond acutely to changes in blood glucose and insulin. Nutritional state also has a marked effect on both the level of circulating leptin protein and leptin gene expression. The aim of this study was to assess whether the prior nutritional state altered the leptin secretory response to an acute glucose challenge, and to determine potential mechanisms.
Design: Male fed or fasted rats (200-250 g) were administered a single intravenous glucose bolus (1, 4 or 7 g/kg). The serum leptin, glucose, insulin and free fatty acid responses were studied over the following 5 h. The level of leptin gene expression and leptin protein was then determined in the epididymal fat pads, and in fed and fasted untreated rats for basal comparison.
Results: Leptin secretion in response to glucose was suppressed in fasted rats following all glucose doses. The total leptin response was correlated with the total insulin response in all conditions (r = 0.85) and with the glucose response in fed rats (r = 0.69). Both leptin gene expression and leptin protein content were lower in basal fasted rats. Leptin gene expression and leptin protein content still remained lower 5 h following a glucose bolus but there was partial reversal of the effects of fasting following the 7 g/kg glucose dose.
Conclusions: Leptin secretion in response to an intravenous glucose bolus was determined by the insulin response and was significantly suppressed in fasted compared to fed rats. In addition to differences in the total insulin response of the animals, lower leptin responses may be facilitated by lower levels of both leptin gene mRNA and pre-existing leptin protein in epididymal adipose tissue of fasted rats.