Mitochondria: a possible nexus for the regulation of energy homeostasis by the endocannabinoid system?

2014 ◽  
Vol 307 (1) ◽  
pp. E1-E13 ◽  
Author(s):  
Christopher Lipina ◽  
Andrew J. Irving ◽  
Harinder S. Hundal
Keyword(s):  
Energy Homeostasis ◽  
Endocannabinoid System ◽  
Oxidative Capacity ◽  
Current Evidence ◽  
Peripheral Insulin Resistance ◽  
Physiological Processes ◽  
Peripheral Stimulation ◽  
The Metabolic Syndrome ◽  
Lipid Utilization

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.

The Role of Endocannabinoid System Blockade in the Treatment of the Metabolic Syndrome

2007 ◽  
Vol 47 (5) ◽  
pp. 642-652 ◽  
Author(s):  
Anna I. Kakafika ◽  
Dimitri P. Mikhailidis ◽  
Asterios Karagiannis ◽  
Vasilios G. Athyros
Keyword(s):  
Metabolic Syndrome ◽  
Endocannabinoid System ◽  
The Metabolic Syndrome

scholarly journals Variations in Adipokine GenesAdipoQ,Lep, andLepRAre Associated with Risk for Obesity-Related Metabolic Disease: The Modulatory Role of Gene-Nutrient Interactions

2011 ◽  
Vol 2011 ◽  
pp. 1-17 ◽  
Author(s):  
Jennifer Emily Enns ◽  
Carla G. Taylor ◽  
Peter Zahradka
Keyword(s):  
Metabolic Disease ◽  
Energy Homeostasis ◽  
Leptin Receptor ◽  
Disease Risk ◽  
Critical Role ◽  
Nucleotide Polymorphisms ◽  
Nutrient Interactions ◽  
The Metabolic Syndrome ◽  
Susceptible Populations

Obesity rates are rapidly increasing worldwide and facilitate the development of many related disease states, such as cardiovascular disease, the metabolic syndrome, type 2 diabetes mellitus, and various types of cancer. Variation in metabolically important genes can have a great impact on a population's susceptibility to becoming obese and/or developing related complications. The adipokines adiponectin and leptin, as well as the leptin receptor, are major players in the regulation of body energy homeostasis and fat storage. This paper summarizes the findings of single nucleotide polymorphisms in these three genes and their effect on obesity and metabolic disease risk. Additionally, studies of gene-nutrient interactions involving adiponectin, leptin, and the leptin receptor are highlighted to emphasize the critical role of diet in susceptible populations.

scholarly journals Role of N-Linked Glycosylation in PKR2 Trafficking and Signaling

2021 ◽  
Vol 15 ◽  
Author(s):  
Jissele A. Verdinez ◽  
Julien A. Sebag
Keyword(s):  
Plasma Membrane ◽  
Energy Homeostasis ◽  
Reproductive Function ◽  
Receptor Trafficking ◽  
Membrane Localization ◽  
Accessory Protein ◽  
Post Translational Modification ◽  
Physiological Processes ◽  
Glycosylation Sites

Prokineticin receptors are GPCRs involved in several physiological processes including the regulation of energy homeostasis, nociception, and reproductive function. PKRs are inhibited by the endogenous accessory protein MRAP2 which prevents them from trafficking to the plasma membrane. Very little is known about the importance of post-translational modification of PKRs and their role in receptor trafficking and signaling. Here we identify 2 N-linked glycosylation sites within the N-terminal region of PKR2 and demonstrate that glycosylation of PKR2 at position 27 is important for its plasma membrane localization and signaling. Additionally, we show that glycosylation at position 7 results in a decrease in PKR2 signaling through Gαs without impairing Gαq/11 signaling.

Abnormalities in neuroendocrine stress response in psychosis: the role of endocannabinoids

2015 ◽  
Vol 46 (1) ◽  
pp. 27-45 ◽  
Author(s):  
E. Appiah-Kusi ◽  
E. Leyden ◽  
S. Parmar ◽  
V. Mondelli ◽  
P. McGuire ◽  
...  
Keyword(s):  
Stress Response ◽  
Hpa Axis ◽  
Psychotic Disorders ◽  
Endocannabinoid System ◽  
Current Evidence ◽  
Response To Stress ◽  
Health And Disease ◽  
Stress Response System ◽  
Precise Role

The aim of this article is to summarize current evidence regarding alterations in the neuroendocrine stress response system and endocannabinoid system and their relationship in psychotic disorders such as schizophrenia. Exposure to stress is linked to the development of a number of psychiatric disorders including psychosis. However, the precise role of stress in the development of psychosis and the possible mechanisms that might underlie this are not well understood. Recently the cannabinoid hypothesis of schizophrenia has emerged as a potential line of enquiry. Endocannabinoid levels are increased in patients with psychosis compared with healthy volunteers; furthermore, they increase in response to stress, which suggests another potential mechanism for how stress might be a causal factor in the development of psychosis. However, research regarding the links between stress and the endocannabinoid system is in its infancy. Evidence summarized here points to an alteration in the baseline tone and reactivity of the hypothalamic–pituitary–adrenal (HPA) axis as well as in various components of the endocannabinoid system in patients with psychosis. Moreover, the precise nature of the inter-relationship between these two systems is unclear in man, especially their biological relevance in the context of psychosis. Future studies need to simultaneously investigate HPA axis and endocannabinoid alterations both at baseline and following experimental perturbation in healthy individuals and those with psychosis to understand how they interact with each other in health and disease and obtain mechanistic insight as to their relevance to the pathophysiology of schizophrenia.

scholarly journals mTOR Pathway is Involved in Energy Homeostasis Regulation as a Part of the Gut–Brain Axis

2020 ◽  
Vol 21 (16) ◽  
pp. 5715
Author(s):  
Veronica Pena-Leon ◽  
Raquel Perez-Lois ◽  
Luisa Maria Seoane
Keyword(s):  
Energy Homeostasis ◽  
The Body ◽  
Mtor Signaling ◽  
Physiological Processes ◽  
Energy Sensor ◽  
Relevant Role ◽  
Regulate Food Intake ◽  
Glucose And Lipid Homeostasis ◽  
Treatment Of Obesity

Mammalian, or mechanic, target of rapamycin (mTOR) signaling is a crucial factor in the regulation of the energy balance that functions as an energy sensor in the body. The present review explores how the mTOR/S6k intracellular pathway is involved in modulating the production of different signals such as ghrelin and nesfatin-1 in the gastrointestinal tract to regulate food intake and body weight. The role of gastric mTOR signaling in different physiological processes was studied in depth through different genetic models that allow the modulation of mTOR signaling in the stomach and specifically in gastric X/A type cells. It has been described that mTOR signaling in X/A-like gastric cells has a relevant role in the regulation of glucose and lipid homeostasis due to its interaction with different organs such as liver and adipose tissue. These findings highlight possible therapeutic strategies, with the gut–brain axis being one of the most promising targets in the treatment of obesity.

scholarly journals The fundamental role of the endocannabinoid system in endometrium and placenta: implications in pathophysiological aspects of uterine and pregnancy disorders

2020 ◽  
Vol 26 (4) ◽  
pp. 586-602 ◽  
Author(s):  
J Maia ◽  
BM Fonseca ◽  
N Teixeira ◽  
G Correia-da-Silva
Keyword(s):  
Endometrial Cancer ◽  
Ectopic Pregnancy ◽  
Fallopian Tube ◽  
Biological Activities ◽  
Acid Amide ◽  
Endocannabinoid System ◽  
Metabolic Enzymes ◽  
Current Evidence ◽  
Original Research

Abstract BACKGROUND The endocannabinoid system (ECS) consists of the cannabinoid receptors CB1 and CB2, the main endocannabinoids anandamide (AEA) and 2-arachidonoylglycerol (2-AG) and their metabolic enzymes N-acylphosphatidylethanolamine-specific phospholipase D, fatty acid amide hydrolase, diacylglycerol lipase and monoacylglycerol lipase. This system is involved in the modulation of essential physiological processes. Its role in the reproductive system has become significantly important in recent years, given its major role in events such as gametogenesis, decidualisation, implantation and placentation. OBJECTIVE AND RATIONALE In this paper, we review the literature and summarize the role of the ECS elements in reproduction and their potential as early markers for diagnosis of reproductive disorders or as pharmacological targets for treatment. SEARCH METHODS Original research and review papers published from 1964 to June 2019 were selected in terms of relevance, reliability and quality by searching PubMed, MEDLINE and Web of Science, using the following search terms: endocannabinoid system and endometriosis; endocannabinoid system and ectopic pregnancy; endocannabinoid system and miscarriage; endocannabinoid system and pre-eclampsia; endocannabinoid system and endometrial cancer; endocannabinoid system and reproduction; endocannabinoid, endometrium; placenta; N-acylethanolamines; anandamide; 2-arachidonoylglycerol; and cannabinoids. OUTCOMES This review demonstrates relevant information concerning ECS alterations in endometriosis, ectopic pregnancy, miscarriage, pre-eclampsia and endometrial cancer. We highlight the importance of the endocannabinoids in endometrial and placental physiology and pathophysiology, from studies in vitro and in vivo and in clinical observations. The most studied of the endogenous cannabinoids is AEA. The levels of AEA were increased in plasma of patients with endometriosis and miscarriage, as well as in the fallopian tube of women with ectopic pregnancy and in endometrial biopsies of endometrial cancer. Changes in the pattern of expression of the cannabinoid receptor CB1 were also observed in endometrial biopsies of endometriosis, fallopian tube and decidua of patients with ectopic pregnancy and pre-eclamptic placenta. Moreover, alterations in CB2 expression have been reported in association with endometrial cancer. In general, studies on the cannabinoid signalling through CB2 and on the biological activities of the other major endocannabinoid, namely 2-AG, as well as its metabolic enzymes are scarce and avidly required. WIDER IMPLICATIONS The pathophysiological mechanisms involved in the described endometrial and placental pathologies are still unclear and lack the means for an early diagnosis. Based on current evidence, though alterations in ECS are demonstrated at tissue level, it is difficult to associate plasmatic changes in AEA with specific endometrial and placental diseases. Thus, pairing alterations in AEA levels with 2-AG and/or other endocannabinoid-like molecules may provide more accurate and early diagnoses. In addition, patients may benefit from new therapies that target the ECS and endocannabinoid signalling.

scholarly journals The Role of Adipose Tissue Mitochondria: Regulation of Mitochondrial Function for the Treatment of Metabolic Diseases

2019 ◽  
Vol 20 (19) ◽  
pp. 4924 ◽  
Author(s):  
Lee ◽  
Park ◽  
Oh ◽  
Lee ◽  
Kim ◽  
...  
Keyword(s):  
Adipose Tissue ◽  
Mitochondrial Function ◽  
Energy Homeostasis ◽  
Metabolic Diseases ◽  
Oxidative Capacity ◽  
Adipose Tissues ◽  
Adaptive Thermogenesis ◽  
Brown Adipose

: Mitochondria play a key role in maintaining energy homeostasis in metabolic tissues, including adipose tissues. The two main types of adipose tissues are the white adipose tissue (WAT) and the brown adipose tissue (BAT). WAT primarily stores excess energy, whereas BAT is predominantly responsible for energy expenditure by non-shivering thermogenesis through the mitochondria. WAT in response to appropriate stimuli such as cold exposure and β-adrenergic agonist undergoes browning wherein it acts as BAT, which is characterized by the presence of a higher number of mitochondria. Mitochondrial dysfunction in adipocytes has been reported to have strong correlation with metabolic diseases, including obesity and type 2 diabetes. Dysfunction of mitochondria results in detrimental effects on adipocyte differentiation, lipid metabolism, insulin sensitivity, oxidative capacity, and thermogenesis, which consequently lead to metabolic diseases. Recent studies have shown that mitochondrial function can be improved by using thiazolidinedione, mitochondria-targeted antioxidants, and dietary natural compounds; by performing exercise; and by controlling caloric restriction, thereby maintaining the metabolic homeostasis by inducing adaptive thermogenesis of BAT and browning of WAT. In this review, we focus on and summarize the molecular regulation involved in the improvement of mitochondrial function in adipose tissues so that strategies can be developed to treat metabolic diseases.

scholarly journals Influence of Trace Elements on Neurodegenerative Diseases of The Eye—The Glaucoma Model

2021 ◽  
Vol 22 (9) ◽  
pp. 4323
Author(s):  
Agnieszka Kamińska ◽  
Giovanni Luca Romano ◽  
Robert Rejdak ◽  
Sandrine Zweifel ◽  
Michal Fiedorowicz ◽  
...  
Keyword(s):  
Trace Elements ◽  
Ganglion Cells ◽  
Current Evidence ◽  
Retinal Ganglion ◽  
Ocular Tissues ◽  
Ion Flow ◽  
Physiological Processes ◽  
Axon Loss ◽  
Flow Through

Glaucoma is a heterogeneous group of chronic neurodegenerative disorders characterized by a relatively selective, progressive damage to the retinal ganglion cells (RGCs) and their axons, which leads to axon loss and visual field alterations. To date, many studies have shown the role of various elements, mainly metals, in maintaining the balance of prooxidative and antioxidative processes, regulation of fluid and ion flow through cell membranes of the ocular tissues. Based on the earlier and current research results, their relationship with the development and progression of glaucoma seems obvious and is increasingly appreciated. In this review, we aimed to summarize the current evidence on the role of trace elements in the pathogenesis and prevention of glaucomatous diseases. Special attention is also paid to the genetic background associated with glaucoma-related abnormalities of physiological processes that regulate or involve the ions of elements considered as trace elements necessary for the functioning of the cells.

scholarly journals Monounsaturated Fatty Acids in Obesity-Related Inflammation

2020 ◽  
Vol 22 (1) ◽  
pp. 330
Author(s):  
Gaetan Ravaut ◽  
Alexandre Légiot ◽  
Karl-F. Bergeron ◽  
Catherine Mounier
Keyword(s):  
Fatty Acids ◽  
Chronic Inflammation ◽  
Energy Homeostasis ◽  
Monounsaturated Fatty Acids ◽  
Beneficial Effects ◽  
Reactive Protein ◽  
The Metabolic Syndrome ◽  
Stearoyl Coa Desaturase ◽  
The Impact

Obesity is an important aspect of the metabolic syndrome and is often associated with chronic inflammation. In this context, inflammation of organs participating in energy homeostasis (such as liver, adipose tissue, muscle and pancreas) leads to the recruitment and activation of macrophages, which secrete pro-inflammatory cytokines. Interleukin-1β secretion, sustained C-reactive protein plasma levels and activation of the NLRP3 inflammasome characterize this inflammation. The Stearoyl-CoA desaturase-1 (SCD1) enzyme is a central regulator of lipid metabolism and fat storage. This enzyme catalyzes the generation of monounsaturated fatty acids (MUFAs)—major components of triglycerides stored in lipid droplets—from saturated fatty acid (SFA) substrates. In this review, we describe the molecular effects of specific classes of fatty acids (saturated and unsaturated) to better understand the impact of different diets (Western versus Mediterranean) on inflammation in a metabolic context. Given the beneficial effects of a MUFA-rich Mediterranean diet, we also present the most recent data on the role of SCD1 activity in the modulation of SFA-induced chronic inflammation.

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