scholarly journals SAT-LB100 Central and Peripheral Endocannabinoid Levels in Obese Versus Lean Women

2020 ◽  
Vol 4 (Supplement_1) ◽  
Author(s):  
Mariana Farage-Martins ◽  
Amelio Godoy-Matos ◽  
Denise Pires Carvalho ◽  
Judith Harvey-White ◽  
Rosilene Taveira da Silva

Abstract The endocannabinoid system (ECS) is thought to be involved in obesity because its activation increases appetite and weight gain (Pagotto et al 2006). The ECS is hyperactivated in the hypothalamus of obese mice, and peripheral overactivation has been observed in humans; circulating 2-arachidonoyl glycerol (2-AG) levels positively correlated with body fat, visceral fat and fasting glucose (Osei-Hyiaman et al 2005) (Bluher et al 2006) (Motaghedi and McGraw 2008) (Cavuoto et al 2007) (Artmann et al 2008) (Bermudez-Silva 2009). The aim of this study was to evaluate whether differential activation of the peripheral versus the central ECS occurred in humans and to test the hypothesis that the ECS is hyperactivated in the human central nervous system (CNS).Cerebral spinal fluid (CSF) and blood samples were collected from 13 obese and 11 lean control women to measure 2-AG and anandamide (AEA) levels.AEA levels were higher in the plasma of obese women (obese: 4.03 ± 0.91 pmol/mL, N=13; lean: 1.84 ± 0.21 pmol/mL, N=10; p<0.05) but were lower in the CSF of obese women. The plasma/CSF ratio was 41.58 ± 5.78 (N=10) in lean women and 103.0 ± 37.36 (N=6) in obese women (p=0.054). There were no correlations between plasma and CSF AEA levels or with any biochemical parameter. The 2-AG analysis was not possible because of technical problems.Our data suggested that in human obesity, the peripheral ECS may be more active than the central ECS. Indeed, the system appeared to be suppressed in the CNS of obese women. Therefore, the peripheral activation of the ECS may be more relevant for obesity. Keywords: Anandamide, 2-arachidonoyl glycerol, obesity, endocannabinoid, endocannabinoid system, cb1 receptor.

Molecules ◽  
2021 ◽  
Vol 26 (7) ◽  
pp. 1845
Author(s):  
Stephen Schultz ◽  
Georgianna G. Gould ◽  
Nicola Antonucci ◽  
Anna Lisa Brigida ◽  
Dario Siniscalco

Persistent deficits in social communication and interaction, and restricted, repetitive patterns of behavior, interests or activities, are the core items characterizing autism spectrum disorder (ASD). Strong inflammation states have been reported to be associated with ASD. The endocannabinoid system (ECS) may be involved in ASD pathophysiology. This complex network of lipid signaling pathways comprises arachidonic acid and 2-arachidonoyl glycerol-derived compounds, their G-protein-coupled receptors (cannabinoid receptors CB1 and CB2) and the associated enzymes. Alterations of the ECS have been reported in both the brain and the immune system of ASD subjects. ASD children show low EC tone as indicated by low blood levels of endocannabinoids. Acetaminophen use has been reported to be associated with an increased risk of ASD. This drug can act through the ECS to produce analgesia. It may be that acetaminophen use in children increases the risk for ASD by interfering with the ECS.This mini-review article summarizes the current knowledge on this topic.


Healthcare ◽  
2021 ◽  
Vol 9 (6) ◽  
pp. 637
Author(s):  
Shengyan Sun ◽  
Zhaowei Kong ◽  
Qingde Shi ◽  
Haifeng Zhang ◽  
On-Kei Lei ◽  
...  

Objective: The purpose of this study was to evaluate the effects of a 4-week low-carbohydrate diet (LC) with or without exercise training on cardiometabolic health-related profiles in overweight/obese women. Methods: Fifty overweight/obese Chinese women (age: 22.2 ± 3.3 years, body mass index (BMI): 25.1 ± 3.1 kg·m−2) were randomized to either a LC control group (LC-CON, n = 16), a LC and high-intensity interval training group (LC-HIIT, n = 17), or a LC and moderate-intensity continuous training group (LC-MICT, n = 17). All groups consumed LC for 4 weeks, while the LC-HIIT and LC-MICT groups followed an additional five sessions of HIIT (10 × 6 s cycling sprints and 9 s rest intervals, 2.5 min in total) or MICT (cycling continuously at 50–60% of peak oxygen uptake (VO2peak) for 30 min) weekly. Blood pressure, fasting glucose, insulin sensitivity, and several metabolic or appetite regulating hormones were measured before and after intervention. Results: Significant reductions in body weight (− ~2.5 kg, p < 0.001, η2 = 0.772) and BMI (− ~1 unit, p < 0.001, η2 = 0.782) were found in all groups. Systolic blood pressure was reduced by 5–6 mmHg (p < 0.001, η2 = 0.370); fasting insulin, leptin, and ghrelin levels were also significantly decreased (p < 0.05), while insulin sensitivity was improved. However, there were no significant changes in fasting glucose, glucagon, and gastric inhibitory peptide levels. Furthermore, no group differences were found among the three groups, suggesting that extra training (i.e., LC-HIIT and LC-MICT) failed to trigger additional effects on these cardiometabolic profiles. Conclusions: The short-term carbohydrate restriction diet caused significant weight loss and improved blood pressure and insulin sensitivity in the overweight/obese women, although the combination with exercise training had no additional benefits on the examined cardiometabolic profiles. Moreover, the long-term safety and effectiveness of LC needs further study.


Circulation ◽  
2020 ◽  
Vol 142 (Suppl_3) ◽  
Author(s):  
Robin Wilson ◽  
Lakshmi Arivazhagan ◽  
Henry Ruiz ◽  
Jay Pendse ◽  
Laura Frye ◽  
...  

Introduction: The incidence of obesity and its comorbidities is increasing at an alarming rate in US and around the globe. Our previous studies showed that the receptor for advanced glycation end products (RAGE) and its ligands contribute to the pathogenesis of obesity and insulin resistance (IR), as global Ager (gene encoding RAGE) and adipocyte-specific Ager- deleted mice fed a high fat diet (HFD) showed protection from weight gain and IR. However, the role of Ager deletion in mice with established obesity, switched to low fat diet has not been tested. We hypothesize that temporal adipocyte-specific deletion of Ager in obese mice could enhance weight loss and improves glucose homeostasis. Methods: Mice with conditional adipocyte-specific Ager deletion were generated by breeding Ager flox/flox mice with AdipoQ ERT2 Cre recombinase mice resulting in Ager flox/flox / AdipoQ ERT2 Cre (+) and Cre (-) animals. Mice were fed HFD (60% kcal/fat) for 20 weeks starting at 8 weeks of age to establish obesity and were then treated with tamoxifen (TAM) (75 mg/kg per day x 3 alternative days) to induce deletion of Ager . After 4 weeks of TAM treatment, mice were switched to standard chow for 7 weeks and body weight was monitored regularly. Fasting glucose, insulin and glucose tolerance was measured. Results: After 7 weeks of switching to standard chow following TAM, Cre (+) lost significantly more body weight whereas Cre (-) mice showed no significant weight loss over 7 weeks. Furthermore, Cre (+) mice exhibited significantly higher food intake, lower fasting glucose, lower epididymal and inguinal white adipose tissue weights, and improved glucose and insulin tolerance compared to Cre (-) mice. Conclusions: Temporal adipocyte-specific deletion of Ager in mice with established obesity promotes weight loss and improves glucose homeostasis. RAGE may act as a novel therapeutic target in obesity.


2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Abanish Singh ◽  
Michael A. Babyak ◽  
Mario Sims ◽  
Solomon K. Musani ◽  
Beverly H. Brummett ◽  
...  

Abstract In prior work, we identified a novel gene-by-stress association of EBF1’s common variation (SNP rs4704963) with obesity (i.e., hip, waist) in Whites, which was further strengthened through multiple replications using our synthetic stress measure. We now extend this prior work in a precision medicine framework to find the risk group using harmonized data from 28,026 participants by evaluating the following: (a) EBF1 SNPxSTRESS interaction in Blacks; (b) 3-way interaction of EBF1 SNPxSTRESS with sex, race, and age; and (c) a race and sex-specific path linking EBF1 and stress to obesity to fasting glucose to the development of cardiometabolic disease risk. Our findings provided additional confirmation that genetic variation in EBF1 may contribute to stress-induced human obesity, including in Blacks (P = 0.022) that mainly resulted from race-specific stress due to “racism/discrimination” (P = 0.036) and “not meeting basic needs” (P = 0.053). The EBF1 gene-by-stress interaction differed significantly (P = 1.01e−03) depending on the sex of participants in Whites. Race and age also showed tentative associations (Ps = 0.103, 0.093, respectively) with this interaction. There was a significant and substantially larger path linking EBF1 and stress to obesity to fasting glucose to type 2 diabetes for the EBF1 minor allele group (coefficient = 0.28, P = 0.009, 95% CI = 0.07-0.49) compared with the same path for the EBF1 major allele homozygotes in White females and also a similar pattern of the path in Black females. Underscoring the race-specific key life-stress indicators (e.g., racism/discrimination) and also the utility of our synthetic stress, we identified the potential risk group of EBF1 and stress-induced human obesity and cardiometabolic disease.


2010 ◽  
Vol 63 (1-2) ◽  
pp. 33-39 ◽  
Author(s):  
Aleksandra Simoncig-Netjasov ◽  
Svetlana Vujovic ◽  
Miomira Ivovic ◽  
Milina Tancic-Gajic ◽  
Milka Drezgic

Introduction. Hypoestrogenic status in the menopausal women shows a shift to a central android fat distribution and metabolic syndrome (MS). Related metabolic changes and hypertension increase the risk for cardiovascular (CV) diseases. The aim of this study was to investigate the influence of duration of menopause, anthropometric and hormonal parameters on metabolic syndrome. Material and methods. 50 obese women were examined with BMI=31.92?5.83 kg/m2, age 54.40?3.64, time since menopause 5.90?5.46 years. Control group consisted of 37 normal weight women with BMI=23.50?2.13 kg/m2, age 53.92?3.95, time since menopause 5.96?4.92 years. Anthropometric characteristics and blood pressure were measured. Blood was taken at 8 am for: fasting glucose, triglycerides, cholesterol, HDL, LDL, apolipoprotein A (ApoA), apolipoprotein B (ApoB), lipoprotein(a) (Lp(a)), C-reactive protein (CRP), fibrinogen, FSH, LH, prolactin, estradiol, progesterone, testosterone and sex hormone binding globulin (SHBG). Results. In obese women significant negative correlations were found for: BMI and HDL (p<0,05), waist and HDL (p<0,05), FSH and systolic blood pressure (p<0.01), FSH and fasting glucose (p<0,05), LH and waist (p<0.05), SHBG and fasting glucose (p<0.05). A positive correlation was found for lime since meno?pause and waist/hip ratio (p<0.05). In controls positive correlations were found for: waist/hip ratio and systolic and diastolic blood pressure (p<0,05), LH and HDL (p<0.05), estradiol and diastolic blood pressure (p<0,05). Negative correlations were detected for estradiol and waist (p<0,05), time since menopause and HDL (p<0,05). Conclusion. Gaining weight together with menopausal endocrine changes cause metabolic and hemodynamic imbalances, which contribute to risk for cardiovascular diseases.


2015 ◽  
Vol 47 ◽  
pp. 669
Author(s):  
Amanda R. Bonikowske ◽  
Katie C. Carpenter ◽  
Dipankar Bandyopadhyay ◽  
Steven D. Stovitz ◽  
Mark Pereira ◽  
...  

2010 ◽  
Vol 30 (18) ◽  
pp. 6273-6281 ◽  
Author(s):  
F. Massa ◽  
G. Mancini ◽  
H. Schmidt ◽  
F. Steindel ◽  
K. Mackie ◽  
...  

2020 ◽  
Author(s):  
Camila Marchioni ◽  
Bruno Lopes Santos-Lobato ◽  
Maria Eugênia Costa Queiroz ◽  
José Alexandre S. Crippa ◽  
Vitor Tumas

AbstractBackgroundLevodopa-induced dyskinesias (LID) in Parkinson’s disease (PD) are frequent complications, and the endocannabinoid system has a role on its pathophysiology.ObjectiveTo test the hypothesis that the functioning of the endocannabinoid system would be altered in PD and in LID by measuring plasma and CSF levels of α-N-arachidonoylethanolamine (AEA) and 2-arachidonoyl-glycerol (2-AG) in patients with PD with and without LID and in healthy controls.MethodsBlood and CSF samples were collected from 20 healthy controls, 23 patients with PD without LID, and 24 patients with PD with LID. The levels of AEA and 2-AG were measured using a highly sensitive column switching ultrahigh-performance liquid chromatography-tandem mass spectrometry method.ResultsWhen pooled together, patients with PD had lower plasma and CSF levels of 2-AG and higher CSF levels of AEA compared to healthy controls (Mann-Whitney statistics = 303.0, p = 0.02). Patients with PD without LID had lower CSF levels of 2-AG (Kruskal-Wallis statistics = 7.76, p = 0.02) and higher CSF levels of AEA levels than healthy controls (Kruskal-Wallis statistics = 8.81, p = 0.01).ConclusionsThe findings suggest that the endocannabinoid system participates in the pathophysiology of PD symptoms, but its role in the pathophysiology of LID is still unclear.


2021 ◽  
Vol 8 ◽  
Author(s):  
Qi Dai ◽  
Zhi-Xuan Wang ◽  
Yan-Qing Sheng ◽  
Zhi-Wen Wu ◽  
Yan Qiu ◽  
...  

Endocannabinoids play important roles in the functioning of various physiological systems in humans and non-mammalian animals, including invertebrates. However, information concerning their roles in physiological functions in members of the phylum Mollusca is scarce. Here the hypothesis that the endocannabinoids are involved in mediating settlement of marine invertebrates was tested. Two endocannabinoids [N-arachidonoyl ethanolamide (AEA) and 2-arachidonoyl glycerol (2-AG)], and two endocannabinoid-like lipids [N-Oleoylethanolamide (OEA) and N-Palmitoylethanolamide (PEA)] were detected in the green mussel Perna viridis. In particular, 2-AG was present at significantly higher levels in unattached P. viridis compared with attached mussels. The in vivo level of 2-AG was inversely correlated with the attachment activity of P. viridis. Furthermore, exposure to synthetic 2-AG inhibited attachment of P. viridis in a reversible manner. Transcriptomic analysis suggested that up-regulation of 2-AG synthase (Phospholipase C-β, PLC-β) and down-regulation of its degrading enzyme (Monoacylglycerol lipase, MAGL) resulted in higher levels of 2-AG in unattached mussels. A putative mechanism for the negative regulation of mussel attachment by 2-AG is proposed that involves a Ca2+- Nitric oxide (NO)- cyclic guanosine monophosphate (cGMP) pathway. This study broadens our understanding of the evolution and roles of the endocannabinoid system in animals, and reveals an endogenous regulatory cue for mussel attachment.


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