Plasma hyperosmolality stimulates leptin secretion acutely by a vasopressin-adrenal mechanism

Abstract

Levy, James R., and Wayne Stevens. Plasma hyperosmolality stimulates leptin secretion acutely by a vasopressin-adrenal mechanism. Am J Physiol Endocrinol Metab 287: E263-E268, 2004. First published April 6, 2004; 10.1152/ajpendo.00514.2003.-Glucose administration to rodents acutely stimulates leptin secretion. To investigate the mechanism, rats were infused intravenously with various concentrations of glucose, and plasma leptin concentrations were measured with time. The osmolality of the infusates was equalized with various concentrations of carbohydrates that are not metabolized. Hyperosmolar glucose stimulates leptin secretion in a dose-dependent manner, with peak plasma leptin concentrations occurring ϳ3 h after the end of the glucose infusion. Hypertonic infusions of galactose, mannitol, and sodium chloride independently stimulate leptin secretion with approximately one-half the strength of equivalent osmolar concentrations of glucose. Peak plasma leptin concentrations occur ϳ4 h after the end of the hypertonic solution infusion. Hypertonic solutions of mannitol do not stimulate leptin secretion in vasopressindeficient or in adrenalectomized animals. In conclusion, intravenous infusions of hypertonic glucose and hypertonic mannitol independently stimulate leptin secretion. Hyperosmolality stimulates leptin secretion by a vasopressin-adrenal mechanism.LEPTIN IS A HORMONE SECRETED by adipocytes that has pleiotropic functions, including roles in body weight homeostasis, satiety, metabolism, reproduction, and angiogenesis (for review, see Ref. 1). The mechanisms of leptin secretion from adipocytes have been intensively studied. A number of factors, hormones, and conditions regulate leptin secretion. Fasting plasma leptin concentrations are mostly determined by body fat content; numerous investigations have demonstrated that both leptin mRNA and plasma leptin concentrations obtained from animals and humans after an overnight fast are directly proportional to measurements of body fat (6,18,19,27). In addition, leptin secretion is regulated by body fat-independent mechanisms. In rodents and humans, plasma leptin concentration has a diurnal variation that most likely is entrained to meals (4, 23). In the rodent, enteral feeding (26) or the intravenous infusion of total parenteral nutrition or glucose alone (15, 16) causes a rise in plasma leptin concentration ϳ3 h after the calorie bolus. The rise in insulin and the transport and metabolism of energyproducing substrates in adipocytes appear to stimulate postprandial leptin secretion (17,20).We previously showed that leptin secretion from cultured adipocytes was proportional to the uptake and metabolism of glucose and to the intra-adipocyte concentrations of ATP (14). We wanted to determine whether the previous studies in cultured adipocytes could be extended to studies in whole animals. We hypothesized that the intravenous infusion of increasing concentrations of glucose would increase delivery and metabolism of glucose in adipose tissue and acutely increase leptin...

Hyperosmolarity and Increased Serum Sodium Concentration Are Risks for Developing Hypertension Regardless of Salt Intake: A Five-Year Cohort Study in Japan

“…An increase in serum osmolarity by salt has been shown to activate the aldose reductase-fructokinase pathway in the liver and hypothalamus that can over time lead to metabolic syndrome and elevations in blood pressure [3]. The increase in serum and SNS osmolarity stimulates vasopressin and leptin release [34], and the latter can activate the SNS sympathetic response to raise blood pressure [35]. An increase in SNS osmolarity also stimulates the production of cardiotonic steroids (Na-K ATPase) inhibitors that cause peripheral vasoconstriction [36].…”

Mapping Brain Glucose Uptake with Chemical Exchange-Sensitive Spin-Lock Magnetic Resonance Imaging

“…However, this contribution is exaggerated with mannitol, since it remains in the vasculature with a half-life of ∼60 minutes. 22 The osmolality-induced Δ R 1ρ for glucoCESL is dependent on the difference between blood and tissue glucose concentrations. Tissue uptake of Glc and 2DG makes their osmolality contributions to Δ R 1ρ even smaller, since there will be rapid equilibration of blood and tissue glucose concentrations.…”

“…Next, glucoCESL responses were compared for matched doses of Glc, 2DG, and mannitol, and with measurement of arterial blood Glc and 2DG levels. The latter studies served to characterize dynamic properties and to assess Δ R 1ρ contributions from changes in tissue water content after intravenous injection of hypertonic solutions; mannitol served as a control, since it induces large elevations in plasma osmolality, has a long half-life in blood (∼60 minutes in rats 22 ), and does not cross the blood–brain barrier. 23 And lastly, glucoCESL responses were obtained for varied SL power levels at steady-state blood glucose levels to further examine the origin and quantification of glucoCESL responses.…”

Role of leptin in blood pressure regulation and arterial hypertension

“…However, it has been demonstrated that, in rats with chronic mild volume expansion induced by drinking 1% saline, blockade of endogenous leptin with a specific antibody decreases diuresis and natriuresis by 15-20%, suggesting that the renal effect of leptin may be relevant for maintaining Na þ balance [57,60]. In addition, leptin expression in adipose tissue increases in response to a high-salt diet [61] or intravenous infusion of hypertonic NaCl [62] and decreases on low-salt diet [63], as expected for a mediator regulating Na þ balance.…”