Evidence for a decrease in the efficiency of beta-receptor coupling to adenylate cyclase in liver membranes from...

Area of Science:

• Biochemistry
• Cellular Physiology
• Endocrinology

Background:

• Sucrose intake influences factors regulating beta-adrenergic receptors, such as corticosteroids, insulin, and sympathetic nervous system (SNS) tone.
• Previous research indicates a link between dietary factors and beta-adrenergic receptor regulation.

Purpose of the Study:

• To investigate the impact of sucrose feeding on the beta-adrenergic receptor-adenylate cyclase system in rat liver plasma membranes.
• To determine if sucrose affects beta-adrenergic responsiveness and receptor characteristics.

Main Methods:

• Rats were fed a diet supplemented with 10% sucrose solution.
• Beta-adrenergic responsiveness was assessed by measuring isoproterenol-stimulated adenylate cyclase activity.
• Beta-adrenergic receptor characteristics were analyzed using [125I]iodocyanopindolol ([125I]CYP) binding assays.
• Studies were conducted in normal, adrenalectomized (ADX), and 6-hydroxydopamine-pretreated rats.

Main Results:

• Sucrose feeding led to a 50-75% reduction in hepatic isoproterenol-sensitive adenylate cyclase activity.
• This reduction was observed in ADX and 6-hydroxydopamine-pretreated rats, excluding corticosteroids and SNS as sole mediators.
• A decrease in [125I]CYP binding capacity was noted in sucrose-fed ADX rats, suggesting impaired receptor-adenylate cyclase coupling.
• Sucrose feeding reduced activities of phospholipid methyltransferases and S-adenosylmethionine, indicating a potential defect in membrane methylation.

Conclusions:

• Sucrose diet impairs beta-adrenergic receptor to adenylate cyclase coupling efficiency in rat liver membranes.
• The observed effects are independent of corticosteroids and the sympathetic nervous system.
• Diet-induced alterations in membrane methylation pathways may contribute to the decreased beta-adrenergic receptor signaling.