Human adipose tissue binds and metabolizes the endocannabinoids anandamide and 2-arachidonoylglycerol

Spoto, Belinda; Fezza, Filomena; Parlongo, Giovanna; Battista, Natalia; Sgro, E.; Gasperi, Valeria; Zoccali, Carmine; Maccarrone, Mauro

doi:10.1016/j.biochi.2006.07.019

Cited by 70 publications

(62 citation statements)

References 52 publications

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“…Our findings suggest that adipocyte FAAH levels can be considered insulin dependent, suggesting a mechanism as to why adipose FAAH expression is reduced in obese individuals (17). FAAH is localized on extracellular membranes and has been suggested to act on circulating ECs (16). In light of our data, this could explain why circulating EC levels are negatively correlated with insulin sensitivity in humans (27).…”

Section: Diabetes Vol 57 May 2008mentioning

confidence: 54%

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The Role of Adipocyte Insulin Resistance in the Pathogenesis of Obesity-Related Elevations in Endocannabinoids

et al. 2008

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OBJECTIVE-Obesity is associated with an overactive endocannabinoid (EC) system. The mechanisms responsible for increased ECs in obese individuals are poorly understood. Therefore, we examined the role of adipocyte insulin resistance in intracellular EC metabolism.METHODS-We used 3T3-L1 adipocytes and diet-induced obese (DIO) mice to examine the role of obesity and insulin resistance in the regulation and/or dysregulation of intracellular ECs.RESULTS-For the first time, we provide evidence that insulin is a major regulator of EC metabolism. Insulin treatment reduced intracellular ECs (2-arachidonylglycerol [2-AG] and anandamide [AEA]) in 3T3-L1 adipocytes. This corresponded with insulinsensitive expression changes in enzymes of EC metabolism. In insulin-resistant adipocytes, patterns of insulin-induced enzyme expression were disturbed in a manner consistent with elevated EC synthesis and reduced EC degradation. Expression profiling of adipocytes from DIO mice largely recapitulated in vitro changes, suggesting that insulin resistance affects the EC system in vivo. In mice, expression changes of EC synthesis and degradation enzymes were accompanied by increased plasma EC concentrations (2-AG and AEA) and elevated adipose tissue 2-AG.CONCLUSIONS-Our findings suggest that insulin-resistant adipocytes fail to regulate EC metabolism and decrease intracellular EC levels in response to insulin stimulation. These novel observations offer a mechanism whereby obese insulin-resistant individuals exhibit increased concentrations of ECs. Diabetes

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Section: Diabetes Vol 57 May 2008mentioning

confidence: 54%

“…been considered a brain-specific regulatory pathway, evidence suggests that it plays a role in peripheral tissue and, in particular, adipose tissue (16,17,25). This concept is supported by a growing body of literature demonstrating that signaling networks acting in the brain are also relevant in adipose tissue (26).…”

Section: Diabetes Vol 57 May 2008mentioning

confidence: 95%

The Role of Adipocyte Insulin Resistance in the Pathogenesis of Obesity-Related Elevations in Endocannabinoids

et al. 2008

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“…In both mice and humans, CB2R is also present in the main peripheral organs responsible for the control of metabolism, including the liver [18], adipose tissue [5,[19][20][21], skeletal muscle [22] and pancreatic islets [23]. Obesity leads to increased expression of the cannabinoid receptor 2 gene (Cb2 [also known as Cnr2]) both in adipose tissue and liver in high fat fed and ob/ob mice [24].…”

Section: Introductionmentioning

confidence: 99%

Deficiency of CB2 cannabinoid receptor in mice improves insulin sensitivity but increases food intake and obesity with age

et al. 2010

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Aims/hypothesis The endocannabinoid system has a key role in energy storage and metabolic disorders. The endocannabinoid receptor 2 (CB2R), which was first detected in immune cells, is present in the main peripheral organs responsible for metabolic control. During obesity, CB2R is involved in the development of adipose tissue inflammation and fatty liver. We examined the long-term effects of CB2R deficiency in glucose metabolism. Methods Mice deficient in CB2R (Cb2 −/− [also known as Cnr2]) were studied at different ages (2-12 months). Twomonth-old Cb2 −/− and wild-type mice were treated with a selective CB2R antagonist or fed a high-fat diet.Results The lack of CB2R in Cb2 −/− mice led to greater increases in food intake and body weight with age than in Cb2 +/+ mice. However, 12-month-old obese Cb2 −/− mice did not develop insulin resistance and showed enhanced insulin-stimulated glucose uptake in skeletal muscle. In agreement, adipose tissue hypertrophy was not associated with inflammation. Similarly, treatment of wild-type mice with CB2R antagonist resulted in improved insulin sensitivity. Moreover, when 2-month-old Cb2 −/− mice were fed a high-fat diet, reduced body weight gain and normal insulin sensitivity were observed. Conclusions/interpretation These results indicate that the lack of CB2R-mediated responses protected mice from both age-related and diet-induced insulin resistance, suggesting that these receptors may be a potential therapeutic target in obesity and insulin resistance.

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“…O metóxido de sódio, sintetizado a partir de metanol seco e sódio metálico, foi dissolvido na amina e após adicionado o éster metílico ao meio reacional para obtenção das amidas graxas 10,11a-d. De acordo com os resultados obtidos (Tabela 2, entradas [13][14][15][16][17][18][19][20], a utilização do metóxido de sódio proporcionou o aumento da conversão dos ésteres nas amidas graxas, o emprego de menor quantidade estequiométrica da amina e a diminuição da temperatura usada na reação.…”

Section: 46unclassified

“…e também em mamíferos como, por exemplo, em barbatanas de baleias, no fluído cérebro-espinhal de ratos e gatos, no plasma sanguíneo, no tecido adiposo, no cérebro, intestino e outros tecidos de ratos e porcos. [12][13][14][15][16][17][18][19][20][21][22][23] A ocorrência de amidas graxas também foi verificada em organismos unicelulares como, por exemplo, a Corynebacterium nitrilophilus, algumas espécies de Streptomyces e células de câncer de mama. Na cianobactéria marinha Lyngbya majuscula foram identificadas as amidas graxas, hermitamidas, grenadamida, semiplenamidas C e as besar-hanamidas A e B.…”

Section: Introductionunclassified

Síntese de novas amidas graxas a partir da aminólise de ésteres metílicos

et al. 2010

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. Itália km 08 s/n, 96203-000 Rio Grande -RS, Brasil Recebido em 11/11/09; aceito em 17/2/10; publicado na web em 21/5/10 SYNTHESIS OF NEW FATTY ACIDS AMIDES FROM AMINOLYSIS OF FAMES. Recent biochemical and pharmacological studies have led to the characterization of different fatty acid amides as a new family of biologically active lipids. Here, we describe the synthesis of new amides from C16:0, 18:0, 18:1 and 18:1, OH fatty acids (FFA) families with cyclic and acyclic amines and demonstrate for the first time that these compounds produce citotoxic effects. Application of this method to the synthesis of fatty acid amides was performed using the esters aminolysis as a key step and various carboxylic amides were prepared in good yield from fatty acid methyl esters (FAMEs).

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Human adipose tissue binds and metabolizes the endocannabinoids anandamide and 2-arachidonoylglycerol

Cited by 70 publications

References 52 publications

The Role of Adipocyte Insulin Resistance in the Pathogenesis of Obesity-Related Elevations in Endocannabinoids

The Role of Adipocyte Insulin Resistance in the Pathogenesis of Obesity-Related Elevations in Endocannabinoids

Deficiency of CB2 cannabinoid receptor in mice improves insulin sensitivity but increases food intake and obesity with age

Síntese de novas amidas graxas a partir da aminólise de ésteres metílicos

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