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Activation of the Peripheral Endocannabinoid System in Human Obesity
Open accessAbstract
Obesity is the main risk factor for the development of type 2 diabetes. Activation of the central endocannabinoid system increases food intake and promotes weight gain. Blockade of the cannabinoid type 1 (CB-1) receptor reduces body weight in animals by central and peripheral actions; the role of the peripheral endocannabinoid system in human obesity is now being extensively investigated. We measured circulating endocannabinoid concentrations and studied the expression of CB-1 and the main degrading enzyme, fatty acid amide hydrolase (FAAH), in adipose tissue of lean (n = 20) and obese (n = 20) women and after a 5% weight loss in a second group of women (n = 17). Circulating levels of anandamide and 1/2-arachidonoylglycerol were increased by 35 and 52% in obese compared with lean women (P < 0.05). Adipose tissue mRNA levels were reduced by -34% for CB-1 and -59% for FAAH in obese subjects (P < 0.05). A strong negative correlation was found between FAAH expression in adipose tissue and circulating endocannabinoids. Circulating endocannabinoids and CB-1 or FAAH expression were not affected by 5% weight loss. The expression of CB-1 and FAAH was increased in mature human adipocytes compared with in preadipocytes and was found in several human tissues. Our findings support the presence of a peripheral endocannabinoid system that is upregulated in human obesity.
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“and this effect is likely to result from downregulation of FAAH gene expression, an effect which has also been observed in adipocytes sampled from obese women.110”
From Cannabinoids as Pharmacotherapies for Neuropathic Pain: From the Bench to the Bedside (2009) · cites this paper as [110]
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“In a study involving 40 women (Engeli et al., 2005), circulating levels of anandamide and 2-AG were significantly increased in 20 obese versus 20 lean subjects, and remained elevated after a 5% diet-induced weight reduction.”
BackgroundInfluentialSelf-citationAdipose tissue dysfunction in obesity, diabetes, and vascular diseases
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“In such a context, a recent work (60) showed increased circulating levels of AEA and 2-AG in obese women when compared with a lean control group.”
BackgroundInfluentialThe endocannabinoid system links gut microbiota to adipogenesis
Muccioli, G. G., Naslain, D., Bäckhed, F., Reigstad, C. S., Lambert, D. M., Delzenne, N. M., & Cani, P. D. (2010) · Molecular Systems Biology · doi:10.1038/msb.2010.46 · Cited by 691
“On the other hand, obesity is also characterised by greater eCB system tone, that is increased eCB plasma levels, altered expression of the cannabinoid receptor 1 (CB 1 mRNA) and increased eCB levels in adipose tissues”
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Neuroendocrine control of food intake
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“Circulating levels of endogenous cannabinoids are also increased in obese women compared with lean controls [81].”
BackgroundObesity as a risk factor in venous thromboembolism
Stein, P. D., Beemath, A., & Olson, R. E. (2005) · The American Journal of Medicine · doi:10.1016/j.amjmed.2005.03.012 · Cited by 588
Endocrine disrupters as obesogens
Grün, F., & Blumberg, B. (2009) · Molecular and Cellular Endocrinology · doi:10.1016/j.mce.2009.02.018 · Cited by 586
“Elevated endocannabinoid levels are found in obese subjects and correlate with increased visceral fat mass, suggesting that hyperactivity in cannabinoid signaling drives the obesogenic response (Engeli et al., 2005; Bluher et al., 2006).”
The Endocannabinoid System in Energy Homeostasis and the Etiopathology of Metabolic Disorders
Silvestri, C., & Marzo, V. D. (2013) · Cell Metabolism · doi:10.1016/j.cmet.2013.03.001 · Cited by 575
“These results are consistent with in vitro data in L6 rat myotubes in which rimonabant or CB1 knockdown increased glucose uptake, with the former being accompanied by increased expression of phosphatidylinositol 3-kinase (PI3K) catalytic and regulatory subunits and subsequently by AKT and mitochondrial pyruvate dehydr…”
BackgroundResultInfluentialDysregulation of the Peripheral and Adipose Tissue Endocannabinoid System in Human Abdominal Obesity
Blüher, M., Engeli, S., Klöting, N., Berndt, J., Faßhauer, M., Bátkai, S., Pacher, P., Schön, M. R., Jordan, J., & Stümvoll, M. (2006) · Diabetes · doi:10.2337/db06-0812 · Cited by 526
“On the other hand, our data for the most part confirm the findings from our first study in women with unknown fat distribution phenotypes but with no concomitant medications, with the same hormonal status, and with only small variation in age (21).”
BackgroundResultInfluentialThe gut microbiota, obesity and insulin resistance
Shen, J., Obin, M. S., & Zhao, L. (2013) · Molecular Aspects of Medicine · doi:10.1016/j.mam.2012.11.001 · Cited by 599
“First, obese individuals have higher plasma and adipose levels of eCBs as well as elevated expression of the CB1 receptor in adipose tissues (Cote et al., 2007; Engeli et al., 2005).”
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Tam, J., Vemuri, K. V., Liu, J., Bátkai, S., Mukhopadhyay, B., Godlewski, G., Osei‐Hyiaman, D., Ohnuma, S., Ambudkar, S. V., Pickel, J. M., et al. (2010) · Journal of Clinical Investigation · doi:10.1172/jci42551 · Cited by 470
Circulating Endocannabinoids: From Whence Do They Come and Where are They Going?
Hillard, C. J. (2017) · Neuropsychopharmacology · doi:10.1038/npp.2017.130 · Cited by 449
Regulation of adipocyte lipolysis
Frühbeck, G., Méndez-Giménez, L., Fernández‐Formoso, J. A., Fernández, S., & Rodrı́guez, A. (2014) · Nutrition Research Reviews · doi:10.1017/s095442241400002x · Cited by 447
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CB 1 and CB 2 Receptor Pharmacology
Howlett, A. C., & Abood, M. E. (2017) · Advances in pharmacology · doi:10.1016/bs.apha.2017.03.007 · Cited by 411
“In this fed state, serum endocannabinoid levels are increased (Engeli et al., 2005; Matias et al., 2006).”
Endocannabinoids and the control of energy balance
Matias, I., & Marzo, V. D. (2006) · Trends in Endocrinology and Metabolism · doi:10.1016/j.tem.2006.11.006 · Cited by 367
The gut microbiome as therapeutic target
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Glycerolipid Metabolism and Signaling in Health and Disease
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“Plasma levels of 2-AG are increased in obese individuals, and it was suggested that this might contribute to orexigenic stimuli and elevated appetite (292, 293).”
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“In addition, obesity is characterized by higher eCB system tone in both humans and rodents (Engeli et al., 2005; Bluher et al., 2006; Matias et al., 2006; Cote et al., 2007; D’Eon et al., 2008; Starowicz et al., 2008; Izzo et al., 2009; Muccioli et al., 2010).”
BackgroundCannabinoids as Pharmacotherapies for Neuropathic Pain: From the Bench to the Bedside
Rahn, E. J., & Hohmann, A. G. (2009) · Neurotherapeutics · doi:10.1016/j.nurt.2009.08.002 · Cited by 305
Multiple pathways involved in the biosynthesis of anandamide
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“However, the dominant role of a single pathway in the stimulated synthesis of AEA could make this pathway a target for drug development, in view of emerging evidence that overactivity of the endocannabinoid system may underlie certain diseases, such as obesity/ metabolic syndrome (Osei-Hyiaman et al., 2005;Engeli et a…”
BackgroundEndocannabinoids and the regulation of their levels in health and disease
Marzo, V. D., & Petrosino, S. (2007) · Current Opinion in Lipidology · doi:10.1097/mol.0b013e32803dbdec · Cited by 294
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“The endocannabinoid system also plays a prominent role in the pathology of diabetes and obesity [136, 137].”
BackgroundCannabinoid receptor signaling in progenitor/stem cell proliferation and differentiation
Galve‐Roperh, I., Chiurchiù, V., Díaz-Alonso, J., Bari, M., Guzmán, M., & Maccarrone, M. (2013) · Progress in Lipid Research · doi:10.1016/j.plipres.2013.05.004 · Cited by 287
“Noteworthy, CB1 receptor expression has been found to change along adipocyte differentiation, being low at the pre-adipocyte stage and high when the adipocytes become mature [164–167].”
BackgroundThe endocannabinoid system in obesity and type 2 diabetes
Marzo, V. D. (2008) · Diabetologia · doi:10.1007/s00125-008-1048-2 · Cited by 280
“Evidence in humans The first evidence of peripheral elevation of EC tone in humans came from studies in overweight/obese women with a binge eating disorder [51] and in obese postmenopausal women [52], in whom elevated blood levels of anandamide only, or both anandamide and 2-AG, respectively, were reported.”
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“The eCB system has been shown to be over-activated during obesity in rodents and humans, with an increased expression of synthesising enzymes and receptors and increased plasma and adipose tissue eCB levels (Engeli et al., 2005; Bluher et al., 2006).”
BackgroundRajesh, M., Bátkai, S., Kechrid, M., Mukhopadhyay, P., Lee, W.-S., Horváth, B., Holovac, E., Çınar, R., Liaudet, L., Mackie, K., et al. (2012) · Diabetes · doi:10.2337/db11-0477 · Cited by 261
“CB1Rs are predominantly expressed in the central nervous system (21), but are also present in cardiovascular and virtually all other peripheral tissues, albeit at much lower levels (24,25).”
BackgroundCannabinoid‐2 receptor mediates protection against hepatic ischemia/reperfusion injury
Bátkai, S., Osei‐Hyiaman, D., Pan, H., El-Assal, O. N., Rajesh, M., Mukhopadhyay, P., Hong, F., Harvey-White, J. D., Jafri, A., Haskó, G., et al. (2007) · The FASEB Journal · doi:10.1096/fj.06-7451com · Cited by 252
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“Studies in obese patients showed that only very rigorous interventions, resulting in considerable loss of body weight and intra-abdominal fat, lead to decreased peripheral endocannabinoid concentrations (42,43).”
BackgroundDeveaux, V., Cadoudal, T., Ichigotani, Y., Teixeira-Clerc, F., Louvet, A., Manin, S., Nhieu, J. T. V., Belot, M., Zimmer, A., Even, P. C., et al. (2009) · PLoS ONE · doi:10.1371/journal.pone.0005844 · Cited by 232
“Recent studies in obese patients have reported elevated circulating levels of the endogenous CB2 ligand 2-arachidonoylglycerol [38] and increased production of the compound by fat cells [39].”
BackgroundSympathetic nervous system in obesity-related hypertension: mechanisms and clinical implications
Kalil, G. Z., & Haynes, W. G. (2011) · Hypertension Research · doi:10.1038/hr.2011.173 · Cited by 234
Endocannabinoids and cannabinoid receptors in ischaemia-reperfusion injury and preconditioning.
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“, 2005d) and liver (Batkai et al., 2001; Engeli et al., 2005; Osei-Hyiaman et al., 2005; TeixeiraClerc et al., 2006).”
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“Endogenous cannabinoids are increased both in sc and visceral adipose tissue (VAT) of obese patients and in diet-induced obese mice (10, 11).”
BackgroundThe Endocannabinoid System: Pivotal Orchestrator of Obesity and Metabolic Disease
Mazier, W., Saucisse, N., Gatta‐Cherifi, B., & Cota, D. (2015) · Trends in Endocrinology and Metabolism · doi:10.1016/j.tem.2015.07.007 · Cited by 214
Emerging role of cannabinoids in gastrointestinal and liver diseases: basic and clinical aspects
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Cardiovascular Disease Under the Influence of Excess Visceral Fat
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“In humans, increased endocannabinoid levels are associated with intra-abdominal obesity (4,5,15,16), type 2 diabetes (5), and binge-eating disorder (6).”
BackgroundSugamura, K., Sugiyama, S., Nozaki, T., Matsuzawa, Y., Izumiya, Y., Miyata, K., Nakayama, M., Kaikita, K., Obata, T., Takeya, M., et al. (2008) · Circulation · doi:10.1161/circulationaha.108.811992 · Cited by 198
“Age (mean), y 61.714.9 63.011.6 0.76 Men/women, n 11/9 15/5 0.32 Smoking, n (%) 1 (5) 5 ( 25 ) 0.16 Hypertension, n (%) 12 (60) 16 (80) 0.30 BMI, kg/m”
InfluentialEndocannabinoid Dysregulation in the Pancreas and Adipose Tissue of Mice Fed With a High‐fat Diet
Starowicz, K., Cristino, L., Matias, I., Capasso, R., Racioppi, A., Izzo, A. A., & Marzo, V. D. (2008) · Obesity · doi:10.1038/oby.2007.106 · Cited by 194
“Also with regard to the effect of obesity on CB1 receptor expression in the adipose tissue, there are discrepant results in the literature, with decreases (10) and no changes (11) in obese patients and increases in rats (30) having been reported to date.”
BackgroundResultPresence of functional cannabinoid receptors in human endocrine pancreas
Bermúdez‐Silva, F. J., Suárez, J., Baixerás, E., Čobo, N., Bautista, D., Cuesta-Muñoz, A. L., Fuentes, E., Juan-Picó, P., Castro, M. J., Milman, G., et al. (2007) · Diabetologia · doi:10.1007/s00125-007-0890-y · Cited by 191
“The endocannabinoids are relevant homeostatic signals whose dysregulation contributes to obesity and type 2 diabetes [6, 13].”
BackgroundThe expression of receptors for endocannabinoids in human and rodent skeletal muscle
Cavuoto, P., McAinch, A. J., Hatzinikolas, G., Janovská, A., Game, P. A., & Wittert, G. (2007) · Biochemical and Biophysical Research Communications · doi:10.1016/j.bbrc.2007.09.099 · Cited by 184
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“Because of this difficulty, commonly the peaks of 2AG and 1AG are summed in quantitative experiments [30,97].”
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“, 2005) and in obese post-menopausal women (Engeli et al., 2005), in whom elevated blood levels of endocannabinoids were reported.”
BackgroundMehrpouya‐Bahrami, P., Chitrala, K. N., Ganewatta, M. S., Tang, C., Murphy, E. A., Enos, R. T., Velázquez, K. T., McCellan, J., Nagarkatti, M., & Nagarkatti, P. S. (2017) · Scientific Reports · doi:10.1038/s41598-017-15154-6 · Cited by 168
“Obesity has been characterized by over-activation of eCB system 13 .”
BackgroundMcPartland, J. M., Guy, G. W., & Marzo, V. D. (2014) · PLoS ONE · doi:10.1371/journal.pone.0089566 · Cited by 168
“[232] measured CB1 and FAAH gene expression, and serum AEA and 2-AG, in obese postmenopausal women.”
BackgroundThe l -α-Lysophosphatidylinositol/ GPR55 System and Its Potential Role in Human Obesity
Moreno‐Navarrete, J. M., Catalán, V., Whyte, L. S., Díaz–Arteaga, A., Vázquez‐Martínez, R., Rotellar, F., Guzmán‐Ruiz, R., Gómez‐Ambrosi, J., Pulido, M. R., Russell, W. R., et al. (2011) · Diabetes · doi:10.2337/db11-0649 · Cited by 161
“Although endocannabinoid levels are increased in obesity (39), data on CB1 gene expression in WAT is controversial because reduced (39), increased (42), or unchanged (43) expression between obese and lean subjects has been reported.”
BackgroundMatias, I., Petrosino, S., Racioppi, A., Capasso, R., Izzo, A. A., & Marzo, V. D. (2008) · Molecular and Cellular Endocrinology · doi:10.1016/j.mce.2008.01.026 · Cited by 163
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“The role played by hepatic and pancreatic CBB1 receptors is an evolving field of study, but there is now evidence that overactivity of the ECS is associated with abdominal obesity and type 2 diabetes.(13-15)”
BackgroundEckardt, K., Sell, H., Taube, A., Koenen, M., Platzbecker, B., Cramer, A., Horrighs, A., Lehtonen, M., Tennagels, N., & Eckel, J. (2008) · Diabetologia · doi:10.1007/s00125-008-1240-4 · Cited by 153
The Endocannabinoid System and Plant-Derived Cannabinoids in Diabetes and Diabetic Complications
Horváth, B., Mukhopadhyay, P., Haskó, G., & Pacher, P. (2011) · American Journal Of Pathology · doi:10.1016/j.ajpath.2011.11.003 · Cited by 152
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“In fact, previous studies have demonstrated that elevated plasma levels of 2-AG are most often found in men with abdominal OB, whereas elevated plasma levels of AEA are observed in post-menopausal women.(19,20) These divergent characteristics of AEA and 2-AG concentrations in individuals with increasing body weight re…”
BackgroundTedesco, L., Valerio, A., Cervino, C., Cardile, A., Pagano, C., Vettor, R., Pasquali, R., Carruba, M. O., Marsicano, G., Lutz, B., et al. (2008) · Diabetes · doi:10.2337/db07-1623 · Cited by 145
“Notably, in adipocytes, CB1 receptor expression increases with cell differentiation (10,11).”
BackgroundThe emerging role of the endocannabinoid system in cardiovascular disease
Pacher, P., & Steffens, S. (2009) · Seminars in Immunopathology · doi:10.1007/s00281-009-0145-8 · Cited by 142
“, myocardium) [11–13], human coronary artery endothelial and smooth muscle cells [14, 15], adipose tissue [16, 17], and the liver [17–19].”
BackgroundEndocannabinoids Measurement in Human Saliva as Potential Biomarker of Obesity
Matias, I., Gatta‐Cherifi, B., Tabarin, A., Clark, S., Lesté-Lasserre, T., Marsicano, G., Piazza, P. V., & Cota, D. (2012) · PLoS ONE · doi:10.1371/journal.pone.0042399 · Cited by 137
“For instance, Engeli and colleagues showed that in obese women fasting circulating endocannabinoid levels were not affected by a 5% weight loss obtained after 13–15 weeks of dietary weight reduction protocol [40].”
BackgroundShould peripheral CB1 cannabinoid receptors be selectively targeted for therapeutic gain?
Kunos, G., Osei‐Hyiaman, D., Bátkai, S., Sharkey, K. A., & Makriyannis, A. (2008) · Trends in Pharmacological Sciences · doi:10.1016/j.tips.2008.10.001 · Cited by 139
“The role of CB1 receptors in the central neural control of appetite [4] and evidence for the tonic activity of the endocannabinoid/CB1 receptor system in obesity [5,6] provide a rationale for the use of CB1 antagonists as antiobesity agents.”
BackgroundLifestyle and Metabolic Syndrome: Contribution of the Endocannabinoidome
Marzo, V. D., & Silvestri, C. (2019) · Nutrients · doi:10.3390/nu11081956 · Cited by 135
“The observed increases in AEA and 2-AG levels appear to be due to changes in expression of adipose tissue-metabolizing enzymes, as the AEA-catabolizing enzyme FAAH was decreased and the 2-AG-anabolizing enzyme DAGLα was increased in the adipose tissue from obese individuals in conjunction with decreased CB1 expression…”
BackgroundAdvances in the Physiology of GPR55 in the Central Nervous System
Marichal‐Cancino, B. A., Fajardo-Valdez, A., Ruiz‐Contreras, A. E., Méndez‐Díaz, M., & Prospero-Garcia, O. E. (2016) · Current Neuropharmacology · doi:10.2174/1570159x14666160729155441 · Cited by 140
“On the other hand, obesity seems to be associated with hyperactivity of the human GPR55/LPI system [71] and the endocannabinoids as anandamide and 2-AG [73].”
BackgroundToxicity of Weight Loss Agents
Yen, M., & Ewald, M. B. (2012) · Journal of Medical Toxicology · doi:10.1007/s13181-012-0213-7 · Cited by 132
Endocannabinoids in adipocytes during differentiation and their role in glucose uptake
Gasperi, V., Fezza, F., Pasquariello, N., Bari, M., Oddi, S., Finazzi‐Agrò, A., & Maccarrone, M. (2006) · Cellular and Molecular Life Sciences · doi:10.1007/s00018-006-6445-4 · Cited by 136
Mallat, A., Teixeira-Clerc, F., Deveaux, V., Manin, S., & Lotersztajn, S. (2011) · British Journal of Pharmacology · doi:10.1111/j.1476-5381.2011.01397.x · Cited by 131
“Thus, in three studies, obese individuals displayed elevated serum levels of 2-AG, compared with lean individuals (Engeli et al., 2005; Bluher et al., 2006; Cote et al., 2007).”
BackgroundThe role of metabolic syndrome in heart failure
Filardi, P. P., Paolillo, S., Costanzo, P., Savarese, G., Trimarco, B., & Bonow, R. O. (2015) · European Heart Journal · doi:10.1093/eurheartj/ehv350 · Cited by 132
“cannabinoids, have been reported to be elevated compared with controls.(39) In an experimental mouse model, DM-induced cardiomyopathy was associated with increased endocannabinoid concentration and receptor expression, leading to increased oxidative stress, inflammation, fibrosis, and apoptosis.”
ResultThe thrifty lipids: endocannabinoids and the neural control of energy conservation
DiPatrizio, N. V., & Piomelli, D. (2012) · Trends in Neurosciences · doi:10.1016/j.tins.2012.04.006 · Cited by 135
The Endocannabinoid System and Energy Metabolism
Bellocchio, L., Cervino, C., Pasquali, R., & Pagotto, U. (2008) · Journal of Neuroendocrinology · doi:10.1111/j.1365-2826.2008.01728.x · Cited by 133
Cota, D. (2007) · Diabetes/Metabolism Research and Reviews · doi:10.1002/dmrr.764 · Cited by 134
“found that plasma anandamide and 2-AG levels were significantly elevated in obese women compared with lean women [98].”
BackgroundZoerner, A. A., Bátkai, S., Suchy, M.-T., Gutzki, F., Engeli, S., Jordan, J., & Tsikas, D. (2011) · Journal of Chromatography B · doi:10.1016/j.jchromb.2011.06.025 · Cited by 124
Dol-Gleizes, F., Paumelle, R., Visentin, V., Marés, A.-M., Desitter, P., Hennuyer, N., Gilde, A. J., Staels, B., Schaeffer, P., & Bono, F. (2008) · Arteriosclerosis Thrombosis and Vascular Biology · doi:10.1161/atvbaha.108.168757 · Cited by 123
Endocannabinoid signaling and food addiction
D’Addario, C., Bonaventura, M. V. M. D., Pucci, M., Romano, A., Gaetani, S., Ciccocioppo, R., Cifani, C., & Maccarrone, M. (2014) · Neuroscience & Biobehavioral Reviews · doi:10.1016/j.neubiorev.2014.08.008 · Cited by 124
“in adipose tissue of obese women (Engeli et al., 2005).”
BackgroundThe Endocannabinoid System and Its Relevance for Nutrition
Maccarrone, M., Gasperi, V., Catani, M. V., Diep, T. A., Dainese, E., Hansen, H. S., & Avigliano, L. (2010) · Annual Review of Nutrition · doi:10.1146/annurev.nutr.012809.104701 · Cited by 122
“Indeed, endocannabinoid levels are increased before the onset of obesity (24), thus indicating that a hyperactive ECS could be a cause rather than a consequence of metabolic disorders.”
BackgroundDysregulation of the Endocannabinoid System in Obesity
Engeli, S. (2008) · Journal of Neuroendocrinology · doi:10.1111/j.1365-2826.2008.01683.x · Cited by 123
Pálóczi, J., Varga, Z. V., Hasko, G., & Pacher, P. (2017) · Antioxidants and Redox Signaling · doi:10.1089/ars.2017.7144 · Cited by 129
“Dysregulation of endocannabinoid production and/or receptor expression have been reported under different pathophysiological conditions, including nociception (2, 290), emotional disorders (80, 114), energy imbalance (59, 81, 305), neurodegenerative diseases (5, 85, 87), cancer (337), diabetes and metabolic disorders…”
BackgroundModulation of the Endocannabinoid System in Cardiovascular Disease
Pacher, P., Mukhopadhyay, P., Rajesh, M., Godlewski, G., Bátkai, S., & Kunos, G. (2008) · Hypertension · doi:10.1161/hypertensionaha.105.063651 · Cited by 123
Role of cannabinoid CB2 receptors in glucose homeostasis in rats
Bermúdez‐Silva, F. J., Sánchez-Vera, I., Suárez, J., Serrano, A., Fuentes, E., Juan-Picó, P., Nadal, Á., & de Fonseca, F. R. (2007) · European Journal of Pharmacology · doi:10.1016/j.ejphar.2007.02.066 · Cited by 120
Biomarkers of Endocannabinoid System Activation in Severe Obesity
Sipe, J. C., Scott, T. M., Murray, S., Harismendy, O., Simon, G. M., Cravatt, B. F., & Waalen, J. (2010) · PLoS ONE · doi:10.1371/journal.pone.0008792 · Cited by 119
“It has become apparent that human obesity is associated with activation of the ECS and with increased levels of ECs in many tissues, as well as in the circulation [17] However, the underlying molecular mechanisms of ECS dysregulation in obesity need clarification to better understand ECS risk factors in obesity and to…”
BackgroundInfluentialMarzo, V. D., Verrijken, A., Hakkarainen, A., Petrosino, S., Mertens, I. L., Lundbom, N. M. I., Piscitelli, F., Westerbacka, J., Soro‐Paavonen, A., Matias, I., et al. (2009) · European Journal of Endocrinology · doi:10.1530/eje-09-0643 · Cited by 117
Peripheral endocannabinoid signaling controls hyperphagia in western diet-induced obesity
Argueta, D. A., & DiPatrizio, N. V. (2017) · Physiology & Behavior · doi:10.1016/j.physbeh.2016.12.044 · Cited by 116
“Furthermore, when compared to normal weight human subjects, plasma levels of 2-AG were elevated in obese women [38], and both 2-AG and anandamide were elevated in saliva of obese male and female subjects [36].”
BackgroundCannabinoids and Endocannabinoids in Metabolic Disorders with Focus on Diabetes
Marzo, V. D., Piscitelli, F., & Mechoulam, R. (2011) · Handbook of experimental pharmacology · doi:10.1007/978-3-642-17214-4_4 · Cited by 121
“2005b), the white adipose tissue (Engeli et al. 2005) and adipocytes (Bensaid et al.”
BackgroundCan we ‘seize’ the gut microbiota to treat epilepsy?
De Caro, C., Iannone, L. F., Citraro, R., Striano, P., De Sarro, G., Constanti, A., Cryan, J. F., & Russo, E. (2019) · Neuroscience & Biobehavioral Reviews · doi:10.1016/j.neubiorev.2019.10.002 · Cited by 110
Fong, T. M., & Heymsfield, S. B. (2009) · International Journal of Obesity · doi:10.1038/ijo.2009.132 · Cited by 111
Köfalvi, A. (2007) · Springer eBooks · doi:10.1007/978-0-387-74349-3 · Cited by 110
Metabolically Healthy Obesity—Heterogeneity in Definitions and Unconventional Factors
Brandão, I., Martins, M. J., & Monteiro, R. (2020) · Metabolites · doi:10.3390/metabo10020048 · Cited by 117
Activation of cannabinoid CB1 receptors induces glucose intolerance in rats
Bermúdez‐Silva, F. J., Serrano, A., Diaz-Molina, F. J., Sánchez-Vera, I., Juan-Picó, P., Nadal, Á., Fuentes, E., & de Fonseca, F. R. (2006) · European Journal of Pharmacology · doi:10.1016/j.ejphar.2005.12.016 · Cited by 109
Matias, I. (2007) · Biochimica et Biophysica Acta (BBA) - Molecular and Cell Biology of Lipids · doi:10.1016/j.bbalip.2007.11.001 · Cited by 109
Bátkai, S., Rajesh, M., Mukhopadhyay, P., Haskó, G., Liaudet, L., Cravatt, B. F., Csiszár, A., Ungvari, Z. I., & Pacher, P. (2007) · American Journal of Physiology-Heart and Circulatory Physiology · doi:10.1152/ajpheart.00373.2007 · Cited by 107
“The natural ligands [endocannabinoids: arachidonoyl ethanolamide or anandamide (AEA) and 2arachidonoylglycerol (2-AG)], similarly to their synthetic analogs, exert various antiinflammatory and other effects mediated through the activation of two known cannabinoid (CB) receptors: the CB1 receptor, which is highly expre…”
BackgroundKunos, G., & Tam, J. (2011) · British Journal of Pharmacology · doi:10.1111/j.1476-5381.2011.01352.x · Cited by 113
“The situation is less clear in human obesity, where CB1 expression was reportedly decreased in subcutaneous fat (Engeli et al., 2005), but increased in visceral fat (Bordicchia et al.”
BackgroundDas, S., & O’Keefe, J. H. (2006) · Current Atherosclerosis Reports · doi:10.1007/s11883-006-0048-2 · Cited by 108
“Intra-abdominal obesity further accentuates the physiologic response to stress-induced hormone disturbances, compelling the person to continue to overeat, which causes further worsening of obesity and hormonal balance [ 50 ].”
BackgroundNakata, M., & Yada, T. (2007) · Regulatory Peptides · doi:10.1016/j.regpep.2007.08.009 · Cited by 113
2-Arachidonoylglycerol Signaling in Forebrain Regulates Systemic Energy Metabolism
Jung, K., Clapper, J. R., Fu, J., D’Agostino, G., Guijarro, A. I., Thongkham, D., Avanesian, A., Astarita, G., DiPatrizio, N. V., Frontini, A., et al. (2012) · Cell Metabolism · doi:10.1016/j.cmet.2012.01.021 · Cited by 107
“First, feeding and obesity regulate the production of two endocannabinoid mediators – 2-arachidonoyl-sn-glycerol (2-AG) and anandamide – in peripheral tissues (Gomez et al., 2002; Engeli et al., 2005; Osei-Hyiaman et al., 2005).”
BackgroundMECHANISMS IN ENDOCRINOLOGY: Endocannabinoids and metabolism: past, present and future
Simon, V., & Cota, D. (2017) · European Journal of Endocrinology · doi:10.1530/eje-16-1044 · Cited by 113
Gatta‐Cherifi, B., Matias, I., Vallée, M., Tabarin, A., Marsicano, G., Piazza, P. V., & Cota, D. (2011) · International Journal of Obesity · doi:10.1038/ijo.2011.165 · Cited by 105
A peripheral endocannabinoid mechanism contributes to glucocorticoid-mediated metabolic syndrome
Bowles, N. P., Karatsoreos, I. N., Li, X., Vemuri, K. V., Wood, J.-A., Li, Z., Tamashiro, K. L., Schwartz, G. J., Makriyannis, A., Kunos, G., et al. (2014) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1421420112 · Cited by 111
“The ability of eCB signaling to regulate metabolic function is clearly a complex process that involves many sites of action (12, 13).”
BackgroundEndocannabinoids and the Control of Energy Homeostasis
Kunos, G., Osei‐Hyiaman, D., Liu, J., Godlewski, G., & Bátkai, S. (2008) · Journal of Biological Chemistry · doi:10.1074/jbc.r800012200 · Cited by 112
Russo, P., Strazzullo, P., Cappuccio, F. P., Trégouët, D., Lauria, F., Loguercio, M., Barba, G., Versiero, M., & Siani, A. (2007) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2006-2523 · Cited by 107
“In the last years, a wealth of data indicated that the endogenous cannabinoid system is also an important homeostatic modulator of energy balance and weight control through appetite-stimulating mechanisms as well as other physiological pathways, such as peripheral lipogenesis (17, 18).”
BackgroundFanelli, F., Lallo, V. D. D., Belluomo, I., IASIO, R. D., Baccini, M., Casadio, E., Gasparini, D. I., Colavita, M., Gambineri, A., Grossi, G., et al. (2011) · Journal of Lipid Research · doi:10.1194/jlr.m021378 · Cited by 105
Enhanced endocannabinoid tone as a potential target of pharmacotherapy
Toczek, M., & Malinowska, B. (2018) · Life Sciences · doi:10.1016/j.lfs.2018.04.054 · Cited by 108
Metadata
- Authors
- Engeli, S., Böhnke, J., Feldpausch, M., Gorzelniak, K., Janke, J., Bátkai, S., Pacher, P., Harvey-White, J., Luft, F. C., Sharma, A. M., & Jordan, J.
- Affiliations
- Helios Hospital Berlin-Buch (DE)
- Franz Volhard Clinical Research Center, Charité Campus Buch, and HELIOS Klinikum Berlin, Berlin, Germany
- Laboratory of Physiologic Studies, National Institute on Alcohol Abuse & Alcoholism, National Institutes of Health, Bethesda, Maryland
- National Institutes of Health (US)
- McMaster University (CA)
- Venue
- Diabetes
- Publisher
- American Diabetes Association
- Published
- 2005-10-01
- Volume
- 54
- Issue
- 10
- Pages
- 2838-2843
- ISSN
- 0012-1797 (ISSN-L)
- 1939-327X
- PMC
- PMC2228268
- OpenAlex
- W2162112945
- Cited by
- 686
- References
- 37
- Citations by year
- 2026: 11 · 2025: 14 · 2024: 20 · 2023: 19 · 2022: 20 · 2021: 30 · 2020: 29 · 2019: 24 · 2018: 30 · 2017: 30 · 2016: 15 · 2015: 31 · 2014: 29 · 2013: 29 · 2012: 33
- FWCI
- 38.06
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Diabetes (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- MDC Repository (Max-Delbrueck-Center for Molecular Medicine) (submittedVersion)
- Funders
- Sanofi
- Bundesministerium für Bildung und Forschung
- National Institutes of Health
- National Institute on Alcohol Abuse and Alcoholism (Z01AA000375)
- Topics
- Health Sciences › Medicine › Pharmacology (medical) › Cannabis and Cannabinoid Research
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Adipokines, Inflammation, and Metabolic Diseases
- Life Sciences › Neuroscience › Endocrine and Autonomic Systems › Regulation of Appetite and Obesity
- Keywords
- obesity, cannabinoid type 1 receptor, fatty acid amide hydrolase, anandamide, 2-arachidonoylglycerol, adipose tissue, weight loss, human adipocytes, type 2 diabetes risk
- MeSH terms
- Fatty Acid Amide Hydrolases, Adipose Tissue, Amidohydrolases, Arachidonic Acids, Body Composition, Female, Glycerides, Humans, Middle Aged, Obesity, RNA, Messenger, Weight Loss, Gene Expression, Body Mass Index, Linear Models, Postmenopause, Reverse Transcriptase Polymerase Chain Reaction, Receptor, Cannabinoid, CB1, Polyunsaturated Alkamides, Cannabinoid Receptor Modulators, Endocannabinoids
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