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CB1 blockade-induced weight loss over 48 weeks decreases liver fat in proportion to weight loss in humans

International Journal of Obesity volume 37, pages 699–703 (2013)Cite this article

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Abstract

Objective:

Studies in mice have suggested that endocannabinoid blockade using the cannabinoid receptor type 1 (CB1) blocker rimonabant prevents obesity-induced hepatic steatosis.

Design and subjects:

To determine effects of rimonabant on liver fat in humans, we measured liver fat content by proton magnetic resonance spectroscopy in 37 subjects who used either a CB1 blocker rimonabant or placebo in a double-blind, randomized manner. This was retrospectively compared with a historical hypocaloric diet weight loss group (n=23).

Results:

Weight loss averaged 8.5±1.4 kg in the rimonabant, 1.7±1.0 kg in the placebo and 7.5±0.2 kg in the hypocaloric diet group (P<0.001, rimonabant vs placebo; NS, rimonabant vs hypocaloric diet). Liver fat decreased more in the rimonabant (5.9% (2.5–14.6%) vs 1.8% (0.9–3.5%), before vs after) than in the placebo group (6.8% (2.2–15.7%) vs 4.9% (1.6–7.8%), before vs after, P<0.05). The percentage change in body weight correlated closely with the percentage loss of liver fat (r=0.70, P>0.0001). The decreases in liver fat were comparable between the rimonabant and the young historical hypocaloric diet groups.

Conclusions:

We conclude that, unlike in mice, in humans rimonabant decreases liver fat in proportion to weight loss.

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Acknowledgements

This study was supported by research grants from the Academy of Finland, the Sigrid Juselius Foundation and the Novo Nordisk Foundation. This work is part of the project ‘Hepatic and adipose tissue functions in the metabolic syndrome’ (www.hepadip.org), which is supported by the European Commission as an Integrated Project under the 6th Framework Program (Contract LSHM-CT-2005–018734). We gratefully acknowledge Katja Sohlo and Pentti Pölönen for excellent technical assistance, and the volunteers for their help.

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Authors and Affiliations

  1. Minerva Foundation Institute for Medical Research, Helsinki, Finland

    R Bergholm, K Sevastianova, A Santos, A Kotronen, M Urjansson, M Tiikkainen & H Yki-Järvinen

  2. Department of Medicine, Division of Diabetes, Helsinki University Central Hospital, Helsinki, Finland

    R Bergholm, K Sevastianova, A Santos, A Kotronen, M Urjansson, M Tiikkainen & H Yki-Järvinen

  3. Department of Radiology, University of Helsinki and HUS Radiology (Helsinki Medical Imaging Center), Helsinki, Finland

    A Hakkarainen, J Lundbom & N Lundbom

  4. Department of Psychiatry, Obesity Research Unit, Helsinki University Central Hospital, Helsinki, Finland

    A Rissanen

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  1. R Bergholm
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Correspondence to K Sevastianova.

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Bergholm, R., Sevastianova, K., Santos, A. et al. CB1 blockade-induced weight loss over 48 weeks decreases liver fat in proportion to weight loss in humans. Int J Obes 37, 699–703 (2013). https://doi.org/10.1038/ijo.2012.116

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