Differential alterations of the concentrations of endocannabinoids and related lipids in the subcutaneous adipose tissue of obese diabetic patients

Annuzzi, Giovanni; Piscitelli, Fabiana; Marino, L.; Patti, L.; Giacco, Rosalba; Costabile, Giuseppina; Bozzetto, Lutgarda; Riccardi, Gabriele; Verde, Roberta; Petrosino, Stefania; Rivellese, Angela Albarosa; Marzo, Vincenzo Di

doi:10.1186/1476-511x-9-43

Cited by 72 publications

(58 citation statements)

References 40 publications

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“…Liver transcriptomic and proteomic analyses related to the ECS also supported a stimulatory effect of HFD on EC tone, as indicated by the marked increase in NAPE-PLD and CB1R expression along with the concomitant decrease in FAAH expression and activity. However, an important finding concerns EC levels in the inguinal AT, which were lowered in all groups after HFD challenge, which is in agreement with previous works (47,49) concerning the impact of HFD on adipose depots of both rodents and humans. Because leptin and insulin were strongly increased after HFD challenge, it might be suggested that the decrease in SCAT EC levels is due to the action of these hormones on EC production, as previously shown (50,51).…”

Section: Discussionsupporting

confidence: 91%

Early Low-Fat Diet Enriched With Linolenic Acid Reduces Liver Endocannabinoid Tone and Improves Late Glycemic Control After a High-Fat Diet Challenge in Mice

Demizieux

Piscitelli²,

Troy-Fioramonti

et al. 2016

Diabetes

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Evidence suggests that alterations of glucose and lipid homeostasis induced by obesity are associated with the elevation of endocannabinoid tone. The biosynthesis of the two main endocannabinoids, N-arachidonoylethanolamine and 2-arachidonoyl-glycerol, which derive from arachidonic acid, is influenced by dietary fatty acids (FAs). We investigated whether exposure to n-3 FA at a young age may decrease tissue endocannabinoid levels and prevent metabolic disorders induced by a later high-fat diet (HFD) challenge. Three-week-old mice received a 5% lipid diet containing lard, lard plus safflower oil, or lard plus linseed oil for 10 weeks. Then, mice were challenged with a 30% lard diet for 10 additional weeks. A low n-6/n-3 FA ratio in the early diet induces a marked decrease in liver endocannabinoid levels. A similar reduction was observed in transgenic Fat-1 mice, which exhibit high tissue levels of n-3 FA compared with wild-type mice. Hepatic expression of key enzymes involved in carbohydrate and lipid metabolism was concomitantly changed. Interestingly, some gene modifications persisted after HFD challenge and were associated with improved glycemic control. These findings indicate that early dietary interventions based on n-3 FA may represent an alternative strategy to drugs for reducing endocannabinoid tone and improving metabolic parameters in the metabolic syndrome.The endocannabinoid (EC) system (ECS) is known to play a crucial role in energy homeostasis. Regulation by this system takes place at the central level by changing food intake (1), and at the peripheral level by the modification of energy metabolism (2). An overactive ECS plays a crucial role in obesity by increasing food intake (3) and lipogenesis (4), by downregulating catabolic reactions (5,6), and by promoting fat accumulation and alteration of glucose homeostasis. As a consequence, treating obesity by decreasing ECS activity has been considered. A pharmacological approach was developed, leading to the commercialization of an inverse agonist of the cannabinoid receptor type-1 (CB1R) rimonabant. However, this drug was withdrawn from the market because of its undesired central nervous system side effects (7). Meanwhile, the downregulation of ECS tone in peripheral tissues involved in energy homeostasis, either with non-brain-penetrant CB1R blockers, or inhibitors of the biosynthesis of endogenous CB1R agonists, is still considered to be a potential approach to counter the adverse events observed in obesity (8).The ECS is defined as a set of endogenous ligands (ECs), synthesized and degraded by specific enzymes and receptors that are able to bind these molecules. It includes two membrane receptors, CB1R and CB2R, and two main endogenous agonists, N-arachidonoyl-ethanolamine (AEA [or anandamide]) and 2-arachidonoyl-glycerol (2-AG). AEA is typically synthesized by the enzyme N-acylphosphatidylethanolamine phospholipase D (NAPE-PLD), although alternative pathways

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Section: Discussionsupporting

confidence: 91%

Early Low-Fat Diet Enriched With Linolenic Acid Reduces Liver Endocannabinoid Tone and Improves Late Glycemic Control After a High-Fat Diet Challenge in Mice

Demizieux

Piscitelli²,

Troy-Fioramonti

et al. 2016

Diabetes

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“…[6][7][8] Recent investigations of the ECs in SAT by Annuzzi el al. 34 in a small sample of obese and lean individuals did not detect significant difference between lean and obese subjects, whereas obese with type 2 diabetes had significant higher AEA and lower 2-AG levels. Concerning the lean and obese individuals their findings were in good agreement with our findings in a large sample size.…”

Section: Discussionmentioning

confidence: 98%

Investigations of the human endocannabinoid system in two subcutaneous adipose tissue depots in lean subjects and in obese subjects before and after weight loss

et al. 2011

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Context: Endocannabinoids (ECs) have a role in obesity by affecting appetite and through peripheral effects. Obesity is associated with a dysregulation of the endocannabinoid system (ECS). Objective: We aimed to determine the ECS in subcutaneous adipose tissue (AT) in obese subject and investigate the influence of diet-induced weight loss on this system. Design: The obese study participants underwent a 12 weeks diet regimen resulting in 10-12% weight loss. All study participants underwent fasting blood samples and AT biopsies from abdomen and gluteal region, the obese subjects both before and after weight loss. Setting and participants: A total of 21 healthy obese individuals (10 men/11 women, age 39.5 ± 1.6 years, body mass index (BMI): 37.5±0.8 kg m À2 ) and 21 age-and gender-matched lean subjects (BMI: 23.8±0.4 kg m À2 ) were studied. Main outcome measures: The activity of ECS in AT was determined by measuring arachidonoyl glycerol (2-AG) and N-arachidonoylethanolamine/anandamide in AT by mass spectrometry and gene expressions of enzymes and receptors involved in the ECS. Results: The EC, 2-AG was reduced in obese individuals in the gluteal AT depot (Po0.01). Moreover, 2-AG increased in both depots in the obese subjects following weight loss (Po0.05). The gene expression of the CB1 was either not affected by the obese state (in the gluteal AT depot) or reduced (in the abdominal depot, Po0.05) and significantly affected by weight loss. The expression of the degrading enzymes FAAH, FAAH2, MGL and MGL2 was differently affected by obesity, AT depot and weight loss. Conclusion: We found reduced levels of 2-AG in subcutaneous AT in obesity, which increased after weight loss. In abdominal AT, the low CB1 expression was normalised after weight loss, whereas in gluteal AT the CB1 expression was reduced after weight loss. These findings support the concept of a dysregulated ECS in AT in association with obesity.

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“…It participates in food intake, energy balance, lipid and glucose metabolism [13][14][15][16][17][18]. It also influences the hypothalamic-pituitary axis by decreasing serum LH levels and modulating GnRH secretion.…”

Section: Discussionmentioning

confidence: 99%

“…The endocannabinoid system contributes to human energy homeostasis and plays a role in lipid and carbohydrate metabolism and also in fat accumulation in liver and muscles [13][14][15][16]. Its key factors are the cannabinoid receptors that are expressed in a variety of tissues including the adipose tissue, liver, skeletal muscle, brain, gastrointestinal tract and pancreas [17].…”

Section: Introductionmentioning

confidence: 99%

Wpływ polimorfizmu genu receptora endokanabinoidowego 1 na parametry antropometryczne i metaboliczne u kobiet z zespołem wielotorbielowatych jajników

Lenarcik-Kabza¹,

Łaczmański²,

Milewicz³

et al. 2014

Endokrynologia Polska

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Introduction: Polycystic ovary syndrome (PCOS) is associated with an increasing number of metabolic comorbidities. About 50% of PCOS patients are obese, and insulin resistance affects up to 70% of these women. The endocannabinoid system contributes to human energy homeostasis. CNR1 is a biological candidate for human obesity and related metabolic disorders. The aim of this study was to determine the relationships between CNR1 polymorphisms and anthropometric and metabolic parameters in PCOS women. Material and methods: 130 women diagnosed with PCOS according to the Rotterdam criteria were recruited. The control group consisted of 70 healthy women. Medical history was taken, and physical examination as well as assessment of anthropometric (body mass, height, waist and hip circumference, BMI, waist-to-hip ratio [WHR]) and metabolic parameters (glucose and insulin, the insulin resistance index HOMA, lipid profile) was carried out. Genetic studies to detect six CNR1 gene polymorphisms were performed. Results: The total cholesterol and low-density lipoprotein (LDL) cholesterol levels in PCOS women carrying T/T genotype of rs2023239 CNR1 polymorphism were higher than in those with C/T and C/C. There were no statistical differences in other metabolic parameters or in the value of BMI and WHR between the variants of rs2023239 CNR1 polymorphism. The other studied polymorphisms of the CNR1 gene were not associated with anthropometric or metabolic parameters in PCOS women. There were no differences in anthropometric or metabolic parameters between the variants of studied polymorphisms of the CNR1 gene in control women. Conclusions: On the basis of our study, it seems that CNR1 polymorphisms are not associated with obesity and metabolic disorders, including insulin resistance, in PCOS women. (Endokrynol Pol 2014; 65 (3): 181-188)

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Differential alterations of the concentrations of endocannabinoids and related lipids in the subcutaneous adipose tissue of obese diabetic patients

Cited by 72 publications

References 40 publications

Early Low-Fat Diet Enriched With Linolenic Acid Reduces Liver Endocannabinoid Tone and Improves Late Glycemic Control After a High-Fat Diet Challenge in Mice

Early Low-Fat Diet Enriched With Linolenic Acid Reduces Liver Endocannabinoid Tone and Improves Late Glycemic Control After a High-Fat Diet Challenge in Mice

Investigations of the human endocannabinoid system in two subcutaneous adipose tissue depots in lean subjects and in obese subjects before and after weight loss

Wpływ polimorfizmu genu receptora endokanabinoidowego 1 na parametry antropometryczne i metaboliczne u kobiet z zespołem wielotorbielowatych jajników

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