Immune-mediated Activation of the Endocannabinoid System in Visceral Adipose Tissue in Obesity

Kempf, Kerstin; Hector, J.; Strate, Tim; Schwarzloh, B.; Rose, B.; Herder, C; Martin, Sorina; Algenstaedt, Petra

doi:10.1055/s-2007-984459

Cited by 44 publications

(38 citation statements)

References 24 publications

(29 reference statements)

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“…Another study confirmed that the ECS is activated in obese visceral adipose tissue and that the obesity-related ECS activation is accompanied by 1 6 elevated expression of the pro-inflammatory cytokine TNF-a, which in turn stimulates ECS activation in vitro [120]. These findings show a strong association between adipose tissue inflammation and ECS activation in obesity, and indicate that a pro-inflammatory state may directly activate the ECS.…”

Section: B In Vivo or Ex Vivo Human Datamentioning

confidence: 64%

The Endocannabinoid System: A Promising Target for the Management of Type 2 Diabetes

Scheen

2009

CPPS

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Conflict of interest :AJ Scheen is a consultant for sanofi-aventis, AstraZeneca, GlaxoSmithKline, and has received lecture fees from sanofi-aventis. 1 SUMMARY (Max 250 words : 250)Type 2 diabetes is closely related to abdominal obesity and is generally associated with other cardiometabolic risk factors, resulting in a high incidence of cardiovascular complications.Several animal and human observations suggest that the endocannabinoid (EC) system is overactivated in presence of abdominal obesity and/or diabetes, and contributes to disturbances of energy balance and metabolism. Not only it regulates the intake of nutrients through central mechanisms located within the hypothalamus and limbic area, but it also intervenes in transport, metabolism and deposit of the nutrients in the digestive tract, liver, adipose tissue, skeletal muscle, and possibly pancreas. Activation of both central and peripheral CB1 receptors promotes weight gain and associated metabolic changes. Conversely, rimonabant, the first selective CB 1 receptor antagonist in clinical use, has been shown to reduce body weight, waist circumference, triglycerides, blood pressure, insulin resistance and C-reactive protein levels, and to increase HDL cholesterol and adiponectin concentrations in both non-diabetic and diabetic overweight/obese patients. In addition, a 0.5-0.7% reduction in glycated hemoglobin (HbA1c) levels was observed in metformin-or sulfonylurea-treated patients with type 2 diabetes and in drug-naïve diabetic patients. Almost half of metabolic changes occurred beyond weight loss, in agreement with direct peripheral effects. Rimonabant was generally well-tolerated, but with a slightly higher incidence of depressed mood disorders, anxiety, nausea and dizziness compared to placebo. New trials are supposed to confirm the potential role of rimonabant (and other CB1 neutral antagonists or inverse agonists) in overweight/obese patients with type 2 diabetes and high risk cardiovascular disease.

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Section: B In Vivo or Ex Vivo Human Datamentioning

confidence: 64%

The Endocannabinoid System: A Promising Target for the Management of Type 2 Diabetes

Scheen

2009

CPPS

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“…A reported inverse correlation between fatty acid amidohydrolase expression in adipose tissue and visceral fat mass in obese individuals (31,32) is also compatible with a lipogenic effect of anandamide, although the underlying mechanisms have not been explored. Additional correlative evidence is the increased adipose tissue ECB content in mice with DIO and in obese humans and a parallel decrease in CB 1 R expression in adipose tissue, which may represent down-regulation secondary to increased receptor activation (29).…”

Section: Endocannabinoid Effects In Adipose Tissuementioning

confidence: 99%

“…Although the nature of the primary stimulus that activates the ECB system in obesity is not clear, macrophage infiltration and inflammatory changes in adipose tissue have been implicated in the associated hepatic steatosis and insulin resistance (35)(36)(37) and appear to correlate with indicators of increased ECB activity in visceral fat from obese individuals (31). Macrophages are a rich source of ECBs (38), the biosynthesis of which is induced by inflammatory stimuli such as bacterial endotoxin (39) and platelet-activating factor (40).…”

Section: Endocannabinoid Effects In Adipose Tissuementioning

confidence: 99%

Endocannabinoids and the Control of Energy Homeostasis

Kunos

Osei‐Hyiaman

Liu

et al. 2008

Journal of Biological Chemistry

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Endocannabinoids (ECBs) are ubiquitous lipid mediators that act through the same G protein-coupled receptors (CB 1 and CB 2 ) that recognize plant-derived cannabinoids. As regulators of metabolism, ECBs are anabolic: they increase the intake, promote the storage, and decrease the expenditure of energy. Recent work indicates that activation of peripheral CB 1 receptors by ECBs plays a key role in the hormonal/metabolic changes associated with obesity/metabolic syndrome and may be targeted for its pharmacotherapy.In mammals, body weight and composition are maintained within a narrow range by the integrated control of energy intake, storage, and expenditure. Several important features of this complex regulatory mechanism have emerged as a result of recent advances. First, there are multiple neurotransmitters and hormones involved in regulating energy metabolism with some degree of redundancy. In the case of appetite-promoting (orexigenic) factors, this can ensure energy balance through compensatory changes even if a component is defective, as in the case of neuropeptide Y (1). Second, many of the mediators involved in the neuronal control of appetitive behavior have also been implicated in the regulation of peripheral energy metabolism and vice versa (2, 3). Third, specialized neurons in the brain can sense nutrient availability, and the brain can affect peripheral metabolism indirectly via neural and hormonal mechanisms (4).What are endocannabinoids (ECBs), 2 and how do they enter this picture? The history of marijuana and its medicinal use go back thousands of years, but the endogenous counterparts of cannabis, the ECBs, have been known for only the last 15 years, their discovery having been triggered by the identification of specific cannabinoid (CB) receptors in the brain (5).ECBs are endogenous ligands of the same G protein-coupled receptors that recognize plant-derived CBs, or phytocannabinoids, and produce similar biological effects (6). Unlike endogenous opioid peptides, currently known ECBs are fatty acid derivatives, with the two most widely studied ECBs being arachidonoylethanolamide (anandamide), and 2-arachidonoylglycerol (2-AG) (5). Both are generated "on demand" via enzymatic cleavage from membrane phospholipid precursors and are thought to act locally as autocrine or paracrine mediators (6). Their action is terminated by enzymatic degradation, with anandamide being selectively metabolized by fatty acid amidohydrolase (7) and 2-AG being degraded primarily by monoglyceride lipase (8).Two subtypes of CB receptors have been identified to date. CB 1 receptors (CB 1 R) present at very high levels in the brain, but also at much lower yet functionally relevant levels in many peripheral tissues, and CB 2 R are expressed primarily by immune and hematopoietic cells (6). Both CB 1 R and CB 2 R couple to the G i/o subtypes of G proteins, but can also activate additional, G protein-independent pathways (6). In addition, anandamide is a low affinity ligand of TRPV1 (vanilloid) receptors (9). The orphan G protein-c...

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“…The biochemical mechanisms underlying aberrant EC levels are not completely understood, but the increased bioavailability in obesity may be the result of both increased synthesis and decreased degradation (29). Several studies revealed a reduction of mRNA expression and/or activity of the AEA-degrading enzyme fatty acid amide hydrolase (9,30,56,76). Furthermore, downregulation of CB1R expression in visceral and subcutaneous adipose tissue of obese patients compared with lean controls has been described (9,30,56).…”

Section: The Peripheral Ec System and Its Dysregulation In Obesitymentioning

confidence: 99%

Role of lipid-derived mediators in skeletal muscle insulin resistance

Taube

Eckardt

Eckel

2009

American Journal of Physiology-Endocrinology and Metabolism

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Immune-mediated Activation of the Endocannabinoid System in Visceral Adipose Tissue in Obesity

Cited by 44 publications

References 24 publications

The Endocannabinoid System: A Promising Target for the Management of Type 2 Diabetes

The Endocannabinoid System: A Promising Target for the Management of Type 2 Diabetes

Endocannabinoids and the Control of Energy Homeostasis

Role of lipid-derived mediators in skeletal muscle insulin resistance

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