title: Mitochondria: a possible nexus for the regulation of energy homeostasis by the endocannabinoid system?
abstract: The endocannabinoid system (ECS) regulates numerous cellular and physiological processes through the activation of receptors targeted by endogenously produced ligands called endocannabinoids. Importantly, this signaling system is known to play an important role in modulating energy balance and glucose homeostasis. For example, current evidence indicates that the ECS becomes overactive during obesity whereby its central and peripheral stimulation drives metabolic processes that mimic the metabolic syndrome. Herein, we examine the role of the ECS in modulating the function of mitochondria, which play a pivotal role in maintaining cellular and systemic energy homeostasis, in large part due to their ability to tightly coordinate glucose and lipid utilization. Because of this, mitochondrial dysfunction is often associated with peripheral insulin resistance and glucose intolerance as well as the manifestation of excess lipid accumulation in the obese state. This review aims to highlight the different ways through which the ECS may impact upon mitochondrial abundance and/or oxidative capacity and, where possible, relate these findings to obesity-induced perturbations in metabolic function. Furthermore, we explore the potential implications of these findings in terms of the pathogenesis of metabolic disorders and how these may be used to strategically develop therapies targeting the ECS.
authors.affiliation: Division of Cell Signalling and Immunology, Sir James Black Centre, College of Life Sciences, University of Dundee, Dundee, Scotland, United Kingdom.
authors.forename: Christopher
authors.initials: C
authors.lastname: Lipina
authors.affiliation: Division of Cell Signalling and Immunology, Sir James Black Centre, College of Life Sciences, University of Dundee, Dundee, Scotland, United Kingdom.
authors.forename: Andrew J
authors.initials: AJ
authors.lastname: Irving
authors.affiliation: Division of Cell Signalling and Immunology, Sir James Black Centre, College of Life Sciences, University of Dundee, Dundee, Scotland, United Kingdom h.s.hundal@dundee.ac.uk.
authors.forename: Harinder S
authors.initials: HS
authors.lastname: Hundal
mesh_terms: D000818:Animals; D063388:Endocannabinoids / Q000378:metabolism*; D004734:Energy Metabolism; D025461:Feedback, Physiological; D006706:Homeostasis; D006801:Humans; D007333:Insulin Resistance; D008659:Metabolic Diseases / Q000378:metabolism*; D008928:Mitochondria / Q000378:metabolism*; D009765:Obesity / Q000378:metabolism*; D043882:Receptors, Cannabinoid / Q000378:metabolism*
chemical_list: D063388:Endocannabinoids; D043882:Receptors, Cannabinoid
keywords: 2-AG; AEA; AMPK; CB1 receptor; endocannabinoid system; insulin; obesity