Circulating Endocannabinoids and Insulin Resistance in Patients with Obstructive Sleep Apnea

Wang, Xiaoya; Yu, Qin; Yue, Hongmei; Zhang, Jiabin; Zeng, Shuang; Cui, Fenfen

doi:10.1155/2016/9782031

Cited by 13 publications

(13 citation statements)

References 30 publications

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“…Insulin receptor activity in liver is negatively modulated by the EC system, as had been previously shown by us and others , due to direct downregulation of receptor tyrosine phosphorylation. Insulin binding causes auto‐phosphorylation of insulin receptors, and IRS proteins are next phosphorylated by the activated insulin receptor, which in turn lead to activation of several downstream signalling molecules necessary for glucose, fat and protein disposal, and the trophic properties of insulin .…”

Section: Discussionsupporting

confidence: 73%

Linoleic acid in diets of mice increases total endocannabinoid levels in bowel and liver: modification by dietary glucose

Ghosh

O’Connell

Carlson

et al. 2019

Obesity Science & Practice

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Summary Aim Linoleic acid (LA) is an essential fatty acid involved in the biosynthesis of arachidonic acid and prostaglandins. LA is known to induce obesity and insulin resistance. In this study, two concentrations of LA with or without added glucose (G) were fed to mice to investigate their effects on endocannabinoid (EC) biology. Materials and Methods Four groups of C57BL/6 mice were provided with diets containing 1% or 8% LA with or without added G (LAG) for 8 weeks. Body weights, food intake, circulating glucose and insulin levels were measured throughout the study. Following euthanasia, plasma, bowel and hepatic ECs, monoacylglycerol lipase and fatty acid amide hydroxylase protein levels (enzymes responsible for EC degradation) and transcriptional activity of PPARα in liver were quantified. Liver was probed for evidence of insulin receptor activity perturbation. Results Increasing dietary LA from 1% to 8% significantly increased circulating, small bowel and hepatic ECs. 1%LAG fed mice had lowest feed efficiency, and only liver levels of both ECs were reduced by addition of G. Addition of G to 1% LA diets resulted in elevated monoacylglycerol lipase and fatty acid amide hydroxylase protein levels ( p < 0.001 and p < 0.001, respectively) in liver due to increased transcriptional activity of PPARα ( p < 0.05). The reduced EC levels with addition of G also correlated with a measure of enhanced insulin action. Conclusion In conclusion, body weight of mice is influenced by the source of calorie intake. Furthermore, tissue EC/g are dependent on tissue‐specific synthesis and degradation that are modulated by dietary LA and G which also influence food efficiency, and down‐stream insulin signalling pathways. The findings could potentially be useful information for weight management efforts in humans.

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Section: Discussionsupporting

confidence: 73%

Linoleic acid in diets of mice increases total endocannabinoid levels in bowel and liver: modification by dietary glucose

Ghosh

O’Connell

Carlson

et al. 2019

Obesity Science & Practice

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“…In men, a PEA inverse relationship with glycemia specifically characterizes young and obese individuals, possibly reflecting the loss of PEA anti-inflammatory function against glucotoxicity [37] . A positive association of AEA with fasting insulin and insulin resistance has been frequently reported [8] , [9] , [18] , [38] , [39] . Conversely, contrasting data have been reported for AEA congeners, as they were found to be not [8] or differentially [21] associated with insulin resistance.…”

Section: Discussionmentioning

confidence: 83%

Profiling plasma N-Acylethanolamine levels and their ratios as a biomarker of obesity and dysmetabolism

Fanelli

Mezzullo

Repaci

et al. 2018

Molecular Metabolism

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ObjectiveN-acylethanolamines play different roles in energy balance; anandamide (AEA) stimulates energy intake and storage, N-palmitoylethanolamide (PEA) counters inflammation, and N-oleoylethanolamide (OEA) mediates anorectic signals and lipid oxidation. Inconsistencies in the association of plasma N-acylethanolamines with human obesity and cardiometabolic risk have emerged among previous studies, possibly caused by heterogeneous cohorts and designs, and by unstandardized N-acylethanolamine measurements. We aimed to characterize changes in the plasma profile, including N-acylethanolamine levels and ratios associated with obesity, menopause in women, and ageing in men, and to define the significance of such a profile as a biomarker for metabolic imbalance.MethodsAdult, drug-free women (n = 103 premenopausal and n = 81 menopausal) and men (n = 144) were stratified according to the body mass index (BMI) into normal weight (NW; BMI: 18.5–24.9 kg/m2), overweight (OW; BMI: 25.0–29.9 kg/m2), and obese (OB; BMI ≥30.0 kg/m2). Anthropometric and metabolic parameters were determined. Validated blood processing and analytical procedures for N-acylethanolamine measurements were used. We investigated the effect of BMI and menopause in women, and BMI and age in men, as well as the BMI-independent influence of metabolic parameters on the N-acylethanolamine profile.ResultsBMI and waist circumference directly associated with AEA in women and men, and with PEA in premenopausal women and in men, while BMI directly associated with OEA in premenopausal women and in men. BMI, in both genders, and waist circumference, in women only, inversely associated with PEA/AEA and OEA/AEA. Menopause increased N-acylethanolamine levels, whereas ageing resulted in increasing OEA relative abundance in men. AEA and OEA abundances in premenopausal, and PEA and OEA abundances in lean menopausal women, were directly associated with hypertension. Conversely, PEA and OEA abundances lowered with hypertension in elderly men. Insulin resistance was associated with changes in N-acylethanolamine ratios specific for premenopausal (reduced PEA/AEA and OEA/AEA), menopausal (reduced OEA/AEA) women and men (reduced OEA/AEA and OEA/PEA). PEA and OEA levels increased with total cholesterol, and OEA abundance specifically increased with HDL-cholesterol. Elevated triglyceride levels were associated with increased N-acylethanolamine levels only in menopausal women.ConclusionsObesity-related N-acylethanolamine hypertone is characterized by imbalanced N-acylethanolamine ratios. The profile given by a combination of N-acylethanolamine absolute levels and ratios enables imbalances to be identified in relationship with different metabolic parameters, with specific relevance according to gender, menopause and age, representing a useful means for monitoring metabolic health. Finally, N-acylethanolamine system appears a promising target for intervention strategies.

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“…Sleep disturbances are actually known to be a risk of obesity (107). Accordingly, plasma AEA is increased in patients suffering from obstructive sleep apnea, a condition that is often associated with obesity (108).…”

Section: The Ecs and Metabolic Disorders In Humansmentioning

confidence: 99%

“…The future: focus on novel therapeutic approaches to modulate the ECS Since the major side effects of drugs like rimonabant were CNS related, one opportunity to move forward could be Plasma AEA ↑ levels (53, 99, 116) ↑ after OGTT vs obese subjects (101) Ø after OGTThyperinsulinemic subjects (101) Ø (101) or ↑ (55) circulating levels ↑ in overweight (108) and obese subjects (144) ↑ in obese subjects (145) ↓ after the meal vs obese subjects (109) Ø after the mealhyperinsulinemic subjects (109) Positively associated with adiposity (133) Salivary AEA ↑ levels (76) Plasma 2-AG ↑ before consumption of favorite food, associated with ↑ levels of ghrelin (110) Positive correlation with BMI and intraabdominal adiposity (100) ↑ levels in insulin-resistant obese women vs insulin-sensitive (102) ↓ after consumption of favorite food (110) ↑ after consumption of favorite food (111) Ø (101) provided by CB 1 R antagonists that are unable to pass the blood-brain barrier (118). Some of these drugs, such as the peripherally restricted CB 1 R inverse agonist JD5037 and the CB 1 R antagonist AM6545 have been shown to reduce obesity, reverse leptin resistance and improve hepatic steatosis, dyslipidemia and insulin resistance in genetically and diet-induced obese mice (63,119,120).…”

Section: The Ecs and Metabolic Disorders In Humansmentioning

confidence: 99%

MECHANISMS IN ENDOCRINOLOGY: Endocannabinoids and metabolism: past, present and future

Simon

Cota

2017

European Journal of Endocrinology

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The endocannabinoid system (ECS), including cannabinoid type 1 and type 2 receptors (CB 1 R and CB 2 R), endogenous ligands called endocannabinoids and their related enzymatic machinery, is known to have a role in the regulation of energy balance. Past information generated on the ECS, mainly focused on the involvement of this system in the central nervous system regulation of food intake, while at the same time clinical studies pointed out the therapeutic efficacy of brain penetrant CB 1 R antagonists like rimonabant for obesity and metabolic disorders. Rimonabant was removed from the market in 2009 and its obituary written due to its psychiatric side effects. However, in the meanwhile a number of investigations had started to highlight the roles of the peripheral ECS in the regulation of metabolism, bringing up new hope that the ECS might still represent target for treatment. Accordingly, peripherally restricted CB 1 R antagonists or inverse agonists have shown to effectively reduce body weight, adiposity, insulin resistance and dyslipidemia in obese animal models. Very recent investigations have further expanded the possible toolbox for the modulation of the ECS, by demonstrating the existence of endogenous allosteric inhibitors of CB 1 R, the characterization of the structure of the human CB 1 R, and the likely involvement of CB 2 R in metabolic disorders. Here we give an overview of these findings, discussing what the future may hold in the context of strategies targeting the ECS in metabolic disease.

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Circulating Endocannabinoids and Insulin Resistance in Patients with Obstructive Sleep Apnea

Cited by 13 publications

References 30 publications

Linoleic acid in diets of mice increases total endocannabinoid levels in bowel and liver: modification by dietary glucose

Linoleic acid in diets of mice increases total endocannabinoid levels in bowel and liver: modification by dietary glucose

Profiling plasma N-Acylethanolamine levels and their ratios as a biomarker of obesity and dysmetabolism

MECHANISMS IN ENDOCRINOLOGY: Endocannabinoids and metabolism: past, present and future

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