Insulin determines leptin responses during a glucose challenge in fed and fasted rats

Abstract

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 ¼ 0.85) and with the glucose response in fed rats (r ¼ 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.

Acute and chronic regulation of leptin synthesis, storage, and secretion by insulin and dexamethasone in human adipose tissue

“…Furthermore, we show that, in addition to the maintaining "basal" or spontaneous release of leptin over the long term, insulin can acutely stimulate the rate of release of preformed (biosynthetically labeled) leptin, as we have previously observed in rat adipose tissue (16). Thus, our data suggest that the insulin stimulation of leptin secretion from a stored intracellular pool may contribute to meal-induced variations in serum leptin levels that are documented in humans as well as rats (3,18,35,36).…”

“…Walker et al (35) found that administration of glucose caused a prompt increase in serum leptin, independent of alterations in leptin mRNA, in fed rats with higher adipose tissue leptin content but not in fasted rats with low adipose tissue leptin content. In addition, the magnitude of ultradian leptin pulses is greater in obese than in lean humans (36), and this could be related to their larger stores of preformed leptin.…”

Leptin secretion is related to glucose-derived lipogenesis in isolated adipocytes

“…22,23 Intracellular leptin was decreased by fasting in isolated rat adipocytes, and this has previously been shown in rat epididymal adipose tissue. 1,24 Thus, both before and during the incubation, the adipocytes of fed rats had an increased capacity to secrete leptin in response to nutritional stimuli.…”

“…Serum leptin responses in fasted rats correlated with a suppressed serum insulin response to the glucose challenges in fasted rats and in the fed rats the leptin response was also governed by the serum insulin. 1 The aim of the current study was to determine if incubation with high insulin and glucose concentrations could reverse the suppression of leptin secretion in adipocytes isolated from fasted rats. As glucose uptake into adipocytes has also been associated with leptin secretion, 12 we examined the role of insulin-regulated glucose metabolism as a mechanism for the observed nutritional regulation of leptin expression, production and secretion.…”

“…Over a range of physiological conditions from fasting (low) to hyperinsulinaemia, serum insulin correlated with leptin levels. [1][2][3][4][5] Insulin may regulate leptin secretion by a number of potential mechanisms either directly or by intermediates of insulin signalling pathways acting on leptin gene (ob) transcription. [6][7][8] It may also increase leptin production directly, either via a global increase in translation rate 6 or a specific increase in the rate of translation of ob mRNA.…”