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The dysregulation of the endocannabinoid system in diabesity—a tricky problem

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Abstract

Endocannabinoids (ECs) are small lipid mediators that play a critical role in energy metabolism. Human studies have shown that the EC tone in peripheral tissues positively correlates with increased adiposity. Furthermore, pharmacological inhibition of EC signaling results in weight loss in humans. However, the mechanisms that cause the dysregulation of the EC system in obesity are not well-understood. Since the clinical utility of currently available EC blockers is severely limited due to their side effects like depression and suicidal ideation that are caused by central effects, it is important to delineate the role of central and peripheral effects of EC signaling in regulating glucose and lipid metabolism.

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Abbreviations

2-AG:

2-arachidonoylglycerol

ACC:

acetyl-CoA carboxylase

AEA:

anandamide

CNS:

central nervous system

DM2:

type 2 diabetes mellitus

ECs:

endocannabinoids

FAAH:

fatty acid amide hydrolase

FAS:

fatty acid synthase

GLUT4:

glucose transporter 4

HSL:

hormone-sensitive lipase

ICV:

intracerebroventricular

KO:

knock-out

LCB1:

hepatocyte-specific CB1 receptor knock-out

LPL:

lipoprotein lipase

MBH:

mediobasal hypothalamus

NE:

norepinephrine

Pepck:

phosphoenolpyruvate kinase

PPARγ:

peroxisome proliferator-activated receptor γ

Srebp1c:

sterol regulatory element-binding protein-1c

UCP2:

uncoupling protein 2

WAT:

white adipose tissue

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Acknowledgments

This work was supported by DK074873 to CB from the National Institutes of Health and a European Foundation for the Study of Diabetes grant to TS. We thank George Kunos for critically reading the manuscript. CB is the recipient of a Junior Faculty Award from the American Diabetes Association.

Competing interests statement

The authors declare that no competing financial interests exist.

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  1. Department of Medicine and Neuroscience, Mount Sinai School of Medicine, One Gustave L. Levy Place, P.O. Box 1055, New York, NY, 10029-6574, USA

    Thomas Scherer & Christoph Buettner

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  1. Thomas Scherer
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  2. Christoph Buettner
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Correspondence to Christoph Buettner.

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Scherer, T., Buettner, C. The dysregulation of the endocannabinoid system in diabesity—a tricky problem. J Mol Med 87, 663–668 (2009). https://doi.org/10.1007/s00109-009-0459-y

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