Starowicz Katarzyna M, Cristino Luigia, Matias Isabel, Capasso Raffaele, Racioppi Alessandro, Izzo Angelo A, Di Marzo Vincenzo
Endocannabinoid Research Group, Consiglio Nazionale delle Ricerche, Pozzuoli, Italy.
Obesity (Silver Spring). 2008 Mar;16(3):553-65. doi: 10.1038/oby.2007.106. Epub 2008 Jan 17.
In mice, endocannabinoids (ECs) modulate insulin release from pancreatic beta-cells and adipokine expression in adipocytes through cannabinoid receptors. Their pancreatic and adipose tissue levels are elevated during hyperglycemia and obesity, but the mechanisms underlying these alterations are not understood.
We assessed in mice fed for up to 14 weeks with a standard or high-fat diet (HFD): (i) the expression of cannabinoid receptors and EC biosynthesizing enzymes (N-acyl-phosphatidyl-ethanolamine-selective phospholipase D (NAPE-PLD) and DAGLalpha) and degrading enzymes (fatty acid amide hydrolase (FAAH) and monoacylglycerol lipase (MAGL)) in pancreatic and adipose tissue sections by immunohistochemical staining; (ii) the amounts, measured by liquid chromatography-mass spectrometry, of the ECs, 2-AG, and anandamide (AEA).
Although CB(1) receptors and biosynthetic enzymes were found mostly in alpha-cells, degrading enzymes were identified in beta-cells. Following HFD, staining for biosynthetic enzymes in beta-cells and lower staining for FAAH were observed together with an increase of EC pancreatic levels. While we observed no diet-induced change in the intensity of the staining of EC metabolic enzymes in the mesenteric visceral fat, a decrease in EC concentrations was accompanied by lower and higher staining of biosynthesizing enzymes and FAAH, respectively, in the subcutaneous fat. No change in cannabinoid receptor staining was observed following HFD in any of the analyzed tissues.
We provide unprecedented information on the distribution of EC metabolic enzymes in the pancreas and adipose organ, where their aberrant expression during hyperglycemia and obesity contribute to dysregulated EC levels.
在小鼠中，内源性大麻素（ECs）通过大麻素受体调节胰腺β细胞的胰岛素释放以及脂肪细胞中脂肪因子的表达。在高血糖和肥胖期间，它们在胰腺和脂肪组织中的水平会升高，但这些改变背后的机制尚不清楚。
我们对喂食标准或高脂饮食（HFD）长达14周的小鼠进行了评估：（i）通过免疫组织化学染色，检测胰腺和脂肪组织切片中大麻素受体以及EC生物合成酶（N-酰基磷脂酰乙醇胺选择性磷脂酶D（NAPE-PLD）和二酰甘油脂肪酶α（DAGLα））和降解酶（脂肪酸酰胺水解酶（FAAH）和单酰甘油脂肪酶（MAGL））的表达；（ii）通过液相色谱-质谱法测量ECs、2-花生四烯酸甘油（2-AG）和花生四烯乙醇胺（AEA）的含量。
虽然CB(1)受体和生物合成酶主要在α细胞中发现，但降解酶在β细胞中被鉴定出来。高脂饮食后，观察到β细胞中生物合成酶的染色以及FAAH的较低染色，同时胰腺中EC水平升高。虽然我们在肠系膜内脏脂肪中未观察到饮食诱导的EC代谢酶染色强度变化，但在皮下脂肪中，EC浓度的降低分别伴随着生物合成酶和FAAH较低和较高的染色。高脂饮食后，在任何分析的组织中均未观察到大麻素受体染色的变化。
我们提供了关于EC代谢酶在胰腺和脂肪器官中分布的前所未有的信息，在高血糖和肥胖期间它们的异常表达导致EC水平失调。
