Cannabinoid receptor 2 as antiobesity target

Inflammation, fat storage, and browning modulation

F. Rossi, G. Bellini, L. Luongo, I. Manzo, S. Tolone, C. Tortora, M. E. Bernardo, A. Grandone, A. Conforti, L. Docimo, B. Nobili, L. Perrone, F. Locatelli, S. Maione, E. Miraglia Del Giudice

Research output: Contribution to journalArticle

16 Citations (Scopus)

Abstract

Context: Obesity is associated with a low-grade inflammatory state and adipocyte (ADP) hyperplasia/ hypertrophy. Obesity inhibits the "browning" of white adipose tissue. Cannabinoid receptor 2 (CB2) agonists reduce food intake and induce antiobesity effect in mice. A common missense CB2 variant, Q63R, causes CB2-reduced function. Objective: To evaluate the influence of CB2 receptor on the modulation of childhood obesity and of ADP activity and morphology. Design: CB2-Q63R variant was analyzed in obese Italian children. The effects of an inflammatory stimulus and those of drugs selectively acting on CB2 were investigated on in vitro ADPs obtained from mesenchymal stem cells of adult healthy donors or from sc adipose biopsies of adult nonobese and obese subjects. Setting: Department of Women, Child and General and Specialist Surgery of the Second University of Naples. Patients or Other Participants: A total of 501 obese Italian children (age 11±2.75). Twelve healthy bone marrow donors (age 36.5±15); and 17 subjects, 7 lean (age 42±10) and 10 obese (age 37.8± 12) underwent sc adipose tissue biopsies. Main Outcome Measures: Effects of CB2 stimulation on adipokine, perilipin, and uncoupling protein-1 expression. Results: The less-functional CB2-R63 variant was significantly associated with a high z-score body mass index. CB2 blockade with AM630 reverse agonist increased inflammatory adipokine release and fat storage and reduced browning. CB2 stimulation with JWH-133 agonist reversed all of the obesity-related effects. Conclusion: CB2 receptor is a novel pharmacological target that should be considered for obesity.

Original languageEnglish
Pages (from-to)3469-3478
Number of pages10
JournalJournal of Clinical Endocrinology and Metabolism
Volume101
Issue number9
DOIs
Publication statusPublished - Sep 1 2016

Fingerprint

Cannabinoid Receptors
Fats
Modulation
Inflammation
Obesity
Adipokines
Biopsy
Adipocytes
Tissue Donors
Cannabinoid Receptor Agonists
Tissue
White Adipose Tissue
Pediatric Obesity
Mesenchymal Stromal Cells
Adenosine Diphosphate
Hypertrophy
Stem cells
Hyperplasia
Adipose Tissue
Surgery

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism
  • Biochemistry
  • Endocrinology
  • Clinical Biochemistry
  • Biochemistry, medical

Cite this

Rossi, F., Bellini, G., Luongo, L., Manzo, I., Tolone, S., Tortora, C., ... Miraglia Del Giudice, E. (2016). Cannabinoid receptor 2 as antiobesity target: Inflammation, fat storage, and browning modulation. Journal of Clinical Endocrinology and Metabolism, 101(9), 3469-3478. https://doi.org/10.1210/jc.2015-4381

Cannabinoid receptor 2 as antiobesity target : Inflammation, fat storage, and browning modulation. / Rossi, F.; Bellini, G.; Luongo, L.; Manzo, I.; Tolone, S.; Tortora, C.; Bernardo, M. E.; Grandone, A.; Conforti, A.; Docimo, L.; Nobili, B.; Perrone, L.; Locatelli, F.; Maione, S.; Miraglia Del Giudice, E.

In: Journal of Clinical Endocrinology and Metabolism, Vol. 101, No. 9, 01.09.2016, p. 3469-3478.

Research output: Contribution to journalArticle

Rossi, F, Bellini, G, Luongo, L, Manzo, I, Tolone, S, Tortora, C, Bernardo, ME, Grandone, A, Conforti, A, Docimo, L, Nobili, B, Perrone, L, Locatelli, F, Maione, S & Miraglia Del Giudice, E 2016, 'Cannabinoid receptor 2 as antiobesity target: Inflammation, fat storage, and browning modulation', Journal of Clinical Endocrinology and Metabolism, vol. 101, no. 9, pp. 3469-3478. https://doi.org/10.1210/jc.2015-4381
Rossi, F. ; Bellini, G. ; Luongo, L. ; Manzo, I. ; Tolone, S. ; Tortora, C. ; Bernardo, M. E. ; Grandone, A. ; Conforti, A. ; Docimo, L. ; Nobili, B. ; Perrone, L. ; Locatelli, F. ; Maione, S. ; Miraglia Del Giudice, E. / Cannabinoid receptor 2 as antiobesity target : Inflammation, fat storage, and browning modulation. In: Journal of Clinical Endocrinology and Metabolism. 2016 ; Vol. 101, No. 9. pp. 3469-3478.
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AU - Bellini, G.

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AU - Manzo, I.

AU - Tolone, S.

AU - Tortora, C.

AU - Bernardo, M. E.

AU - Grandone, A.

AU - Conforti, A.

AU - Docimo, L.

AU - Nobili, B.

AU - Perrone, L.

AU - Locatelli, F.

AU - Maione, S.

AU - Miraglia Del Giudice, E.

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