BACKGROUND: The endocannabinoid system (ECS) is involved in appetite, body weight regulation and metabolism and is a promising target for novel pharmacologic treatments for obesity.Central and peripheral effects of endocannabinoids are mediated through CBI, a G-protein coupled receptor.In adipocytes CBI appears to playa role in regulating lipolysis.We have previously demonstrated that CBl expression is upregulated in visceral (V) compared to subcutaneous (S) adipose tissue (AT) and adipocytes (AC) in animal models of obesity.We therefore tested the hypothesis that CBI was also upregulated in VAT and VAC in obese humans.METHODS: Twenty-two morbidly obese subjects (20F12M, Age 40 ± 8 y, BMI S2 ± 9 kg/m 2 ) provided informed consent for the collection of subcutaneous and visceral adipose tissue samples at the time of elective roux-en-Y gastric bypass surgery.CBI mRNA expression levels were determined using quantitative RT-PCR and normalized to the expression of GAPDH.RESULTS: CB I mRNA expression was significantly higher in VAT compared to SAT (91 ± 2S vs. 74 ± 22 relative units, P < O.OS) and in V AC compared to SAC (30 ± 18 vs.IS ± 11, P < 0.01).CBl mRNA expression levels correlated with CD68 expression levels (a macrophage cell surface marker) in SAT (R = 0.S4, P = 0.01) but not in VAT (R = 0.27, P = 0.22).CBI expression levels also correlated with expression levels of monocyte chemotactic protein-I (MCP-I) and interleukin-6 (1L-6) in SAC (R = 0.74, P < 0.001 and R = 0.S9, P = om, respectively), but did not correlate significantly with MCP-I or 1L-6 in V AC (R = -0.20,P = 0.46 and R = O.4S, P = 0.08).CONCLUSIONS: These results indicate that expression of the endocannabinoid receptor CB I is upregulated in VAT and VAC relative to SAT and SAC in morbidly obese individuals.The beneficial effects of pharmacological CB I blockade to reduce abdominal obesity may be mediated.in part, by direct CB I mediated actions of these drugs on visceral adipocytes.In SAT, but not VAT, CBI expression appears related to the inflammatory phenotype.The effects of pharmacological CB I blockade to reduce markers of low-grade systemic inflammation may occur primarily through CB I mediated actions in this depot.
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