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Endocannabinoid dysregulation in the pancreas and adipose tissue of mice fed with a high-fat diet.
Obesity (Silver Spring) 2008; 16(3):553-65O

Abstract

OBJECTIVE

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.

METHODS AND PROCEDURES

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).

RESULTS

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.

DISCUSSION

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.

Authors+Show Affiliations

Endocannabinoid Research Group, Consiglio Nazionale delle Ricerche, Pozzuoli, Italy.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

18239598

Citation

Starowicz, Katarzyna M., et al. "Endocannabinoid Dysregulation in the Pancreas and Adipose Tissue of Mice Fed With a High-fat Diet." Obesity (Silver Spring, Md.), vol. 16, no. 3, 2008, pp. 553-65.
Starowicz KM, Cristino L, Matias I, et al. Endocannabinoid dysregulation in the pancreas and adipose tissue of mice fed with a high-fat diet. Obesity (Silver Spring). 2008;16(3):553-65.
Starowicz, K. M., Cristino, L., Matias, I., Capasso, R., Racioppi, A., Izzo, A. A., & Di Marzo, V. (2008). Endocannabinoid dysregulation in the pancreas and adipose tissue of mice fed with a high-fat diet. Obesity (Silver Spring, Md.), 16(3), pp. 553-65. doi:10.1038/oby.2007.106.
Starowicz KM, et al. Endocannabinoid Dysregulation in the Pancreas and Adipose Tissue of Mice Fed With a High-fat Diet. Obesity (Silver Spring). 2008;16(3):553-65. PubMed PMID: 18239598.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Endocannabinoid dysregulation in the pancreas and adipose tissue of mice fed with a high-fat diet. AU - Starowicz,Katarzyna M, AU - Cristino,Luigia, AU - Matias,Isabel, AU - Capasso,Raffaele, AU - Racioppi,Alessandro, AU - Izzo,Angelo A, AU - Di Marzo,Vincenzo, Y1 - 2008/01/17/ PY - 2008/2/2/pubmed PY - 2008/5/23/medline PY - 2008/2/2/entrez SP - 553 EP - 65 JF - Obesity (Silver Spring, Md.) JO - Obesity (Silver Spring) VL - 16 IS - 3 N2 - OBJECTIVE: 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. METHODS AND PROCEDURES: 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). RESULTS: 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. DISCUSSION: 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. SN - 1930-7381 UR - https://www.unboundmedicine.com/medline/citation/18239598/Endocannabinoid_dysregulation_in_the_pancreas_and_adipose_tissue_of_mice_fed_with_a_high_fat_diet_ L2 - https://doi.org/10.1038/oby.2007.106 DB - PRIME DP - Unbound Medicine ER -