Plasma Leptin and Insulin Relationships in Obese and Nonobese Humans

Abstract

Hyperinsulinemia. is associated with an overexpression of mRNA for the ob protein leptin in rodent models of genetic obesity, and insulin has been reported to directly stimulate leptin mRNA in rat adipocytes. Human obesity is also associated with increased leptin mRNA as well as plasma levels, but there have been no reports of the effect of insulin on leptin secretion. We, therefore, tested the hypothesis that insulin stimulates leptin secretion in humans. Using a newly developed leptin assay, immunoreactive leptin was measured in fasting and postprandial plasma samples from 27 healthy adults and in samples before and during euglycemic-hyperinsulinemic then stepped hypoglycemic (hourly steps at 85, 75, 65, 55, and 45 mg/dl) clamps from 10 healthy subjects and 11 patients with IDDM. Plasma leptin was correlated (r = 0.84, P = 0.0005) with BMI in obese but not nonobese subjects and with fasting (r = 0.75, P = 0.008) but not postprandial plasma insulin levels. (Leptin levels did not change postprandially.) Euglycemic hyperinsulinemia did not alter leptin levels, nor did hyperinsulinemic hypoglycemia. Thus, because circulating leptin levels are not increased during postprandial hyperinsulinemia or during euglycemic (or hypoglycemic) hyperinsulinemia, we conclude that, at least in the short term, insulin does not increase leptin secretion in humans and that hyperleptinemia in obese individuals is not likely the result of hyperinsulinemia.

Effects of prolonged hyperinsulinemia on serum leptin in normal human subjects.

“…Together, these findings suggested that relatively large increases in serum insulin levels (Ͼ 200 pM) were needed for relatively long periods of time (Ͼ 24 h) before serum leptin levels rose significantly. These results are in accord with reports by several groups, who, with one exception, all failed to find effects of acute (up to 5 h) hyperinsulinemia on leptin levels (10)(11)(12)(13)(14)(15)(16). The sole exception, a study by Utriainen et al (16), reported an ‫ف‬ 50% increase in serum leptin after 4 h of unphysiologic high insulin levels ‫ف(‬ 2,800 pM).…”

“…Possible causes for the precipitous decrease in leptin during fasting include changes in serum insulin and/or glucose concentrations. Insulin, because of its close relationship to appetite and body weight control (9), has been scrutinized by several groups (10)(11)(12)(13)(14)(15)(16). All but one (16) found no acute (up to 5 h) effects of hyperinsulinemia on serum leptin concentrations.…”

Ovarian adipocytokines are associated with early in vitro human embryo development independent of the action of ovarian insulin

“…First, both leptin and adiponectin correlated in opposite directions with body weight and BMI as expected [1,8]. Second, we confirmed that exogenous gonadotropins have a stimulatory effect, either directly or indirectly, on serum leptin levels [23] but had a minimal effect on adiponectin [3].…”

“…First, we measured fasting levels of insulin to minimize prandial fluctuations and fasting levels have been shown to correlate better with leptin [8]. Second, we measured total adiponectin instead of its various polymers.…”

“…However, we would argue that pathological states of metabolism such as obesity and IR are inherently different from those in endocrinologically normal women. There is evidence that at least the insulin leptin relationship is different in normal and obese subjects [8]. Furthermore, leptin at physiological levels is a signal of energy abundance whereas adiponectin can be thought of as functionally the opposite [11].…”