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Horm Metab Res 2012; 44(02): 105-113
DOI: 10.1055/s-0031-1297940
Original Basic
© Georg Thieme Verlag KG Stuttgart · New York

The Major Plant-derived Cannabinoid Δ9-Tetrahydrocannabinol Promotes Hypertrophy and Macrophage Infiltration in Adipose Tissue

A. Wong
1   School of Medical Sciences (Pharmacology) and Bosch Institute, The University of Sydney, NSW, Australia
,
N. Gunasekaran
1   School of Medical Sciences (Pharmacology) and Bosch Institute, The University of Sydney, NSW, Australia
,
D. P. Hancock
2   School of Molecular and Microbial Biosciences, University of Sydney, NSW, Australia
,
G. S. Denyer
2   School of Molecular and Microbial Biosciences, University of Sydney, NSW, Australia
,
L. Meng
2   School of Molecular and Microbial Biosciences, University of Sydney, NSW, Australia
,
J. L. Radford
3   School of Medical Sciences (Pathology) and Bosch Institute, The University of Sydney, NSW, Australia
,
I. S. McGregor
4   School of Psychology, The University of Sydney, NSW, Australia
,
J. C. Arnold
1   School of Medical Sciences (Pharmacology) and Bosch Institute, The University of Sydney, NSW, Australia
› Author Affiliations
Further Information

Publication History

received 14 June 2011

accepted 14 November 2011

Publication Date:
21 December 2011 (online)

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Abstract

Synthetic cannabinoid receptor agonists activate lipoprotein lipase and the formation of lipid droplets in cultured adipocytes. Here we extend this work by examining whether Δ9-tetrahydrocannabinol (THC), a major plant-derived cannabinoid, increases adipocyte size in vivo. Further, possibly as a consequence of hypertrophy, we hypothesize that THC exposure promotes macrophage infiltration into adipose tissue, an inflammatory state observed in obese individuals. Rats repeatedly exposed to THC in vivo had reduced body weight, fat pad weight, and ingested less food over the drug injection period. However, THC promoted adipocyte hypertrophy that was accompanied by a significant increase in cytosolic phosphoenolpyruvate carboxykinase (PEPCK-C) expression, an enzyme important in packaging triglycerides. We also showed that THC induced macrophage infiltration and increased expression of the inflammatory cytokine tumor necrosis factor alpha (TNF-α) in adipose tissue but did not induce apoptosis as measured by TUNEL staining. That THC increased adipocyte cell size in the absence of greater food intake, body weight and fat provides a unique model to explore mechanisms underlying changes in adipocyte size associated with a mild inflammatory state in fat tissue.

Key words

fat - obesity - cannabis - inflammation - TNF-α
 

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