Modulation of Fatty Acid-Induced Skeletal Muscle Inflammation by the Peripheral Endocannabinoid System.
type: CreativeWork
description: The endocannabinoid system (ECS) has classically been known as a major neuromodulatory system of the central nervous system, in which endocannabinoids act as retrograde neurotransmitters that inhibit synaptic activity. However, recent evidence has indicated that the ECS may also play a key role in the control of fuel and energy metabolism through its ability to modulate signalling events within peripheral tissues. There is, for example, mounting evidence that suggests that the ECS becomes dysregulated during obesity and that its pathological over-activation in tissues such as skeletal muscle may promote insulin resistance. There is also growing appreciation that the ECS may modulate the activity of other lipid-regulated signalling systems, which may arise as a consequence of endocannabinoids sharing structural attributes with their congeners that include, for example, fatty acids and their derivatives such as the eicosanoids and prostamides. In this regard, it has long been known that sustained increases in the circulating concentration of fatty acids, especially saturated fatty acids (SFAs), can deleteriously affect signalling processes that impact upon energy balance and fuel metabolism in tissues such as skeletal muscle. In particular, the chronic over-supply of SFAs (e.g. palmitate) has been shown to promote insulin resistance and induce proinflammatory NFκB signalling in skeletal muscle. However, whilst endocannabinoids, acting via specific cell surface cannabinoid (CB1 and CB2) receptors, have been shown to suppress insulin signalling in muscle it remains unknown whether they also stimulate or have the capacity to augment palmitate-induced proinflammatory signaling. Consequently, the aim of this project was to determine what impact endocannabinoids have upon fatty acid-induced NFB signalling in muscle cells and to establish whether cannabinoid receptors have any significant role to play in this process. To address this issue, the effects of the endogenous end…
abstract: The endocannabinoid system (ECS) has classically been known as a major neuromodulatory system of the central nervous system, in which endocannabinoids act as retrograde neurotransmitters that inhibit synaptic activity. However, recent evidence has indicated that the ECS may also play a key role in the control of fuel and energy metabolism through its ability to modulate signalling events within peripheral tissues. There is, for example, mounting evidence that suggests that the ECS becomes dysregulated during obesity and that its pathological over-activation in tissues such as skeletal muscle may promote insulin resistance. There is also growing appreciation that the ECS may modulate the activity of other lipid-regulated signalling systems, which may arise as a consequence of endocannabinoids sharing structural attributes with their congeners that include, for example, fatty acids and their derivatives such as the eicosanoids and prostamides. In this regard, it has long been known that sustained increases in the circulating concentration of fatty acids, especially saturated fatty acids (SFAs), can deleteriously affect signalling processes that impact upon energy balance and fuel metabolism in tissues such as skeletal muscle. In particular, the chronic over-supply of SFAs (e.g. palmitate) has been shown to promote insulin resistance and induce proinflammatory NFκB signalling in skeletal muscle. However, whilst endocannabinoids, acting via specific cell surface cannabinoid (CB1 and CB2) receptors, have been shown to suppress insulin signalling in muscle it remains unknown whether they also stimulate or have the capacity to augment palmitate-induced proinflammatory signaling. Consequently, the aim of this project was to determine what impact endocannabinoids have upon fatty acid-induced NFB signalling in muscle cells and to establish whether cannabinoid receptors have any significant role to play in this process. To address this issue, the effects of the endogenous end…
author: Magill, David
language: eng
date published: 2016
date modified: 2026-07-24T02:08:19Z
provider: University of Dundee
publisher: Networked Digital Library of Theses and Dissertations
type: WebPage
source organization: University of Dundee