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Pro-inflammatory obesity in aged cannabinoid-2 receptor-deficient mice

 
: Schmitz, K.; Mangels, N.; Häussler, A.; Ferreiros, N.; Fleming, I.; Tegeder, I.

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International journal of obesity 40 (2016), No.2, pp.366-379
ISSN: 0307-0565
ISSN: 1476-5497
Deutsche Forschungsgemeinschaft DFG
CRC1039
English
Journal Article
Fraunhofer IME ()

Abstract
BACKGROUND AND OBJECTIVES: Cannabinoid-1 receptor signaling increases the rewarding effects of food intake and promotes the growth of adipocytes, whereas cannabinoid-2 receptor (CB2) possibly opposes these pro-obesity effects by silencing the activated immune cells that are key drivers of the metabolic syndrome. Pro-and anti-orexigenic cannabimimetic signaling may become unbalanced with age because of alterations of the immune and endocannabinoid system.
METHODS: To specifically address the role of CB2 for age-associated obesity, we analyzed metabolic, cardiovascular, immune and neuronal functions in 1.2-1.8-year-old CB2(-/-) and control mice, fed with a standard diet and assessed effects of the CB2 agonist, HU308, during high-fat diet (HFD) in 12-16-week-old mice.
RESULTS: The CB2(-/-) mice were obese with hypertrophy of visceral fat, immune cell polarization toward pro-inflammatory subpopulations in fat and liver and hypertension, as well as increased mortality despite normal blood glucose. They also developed stronger paw inflammation and a premature loss of transient receptor potential responsiveness in primary sensory neurons, a phenomenon typical for small fiber disease. The CB2 agonist HU308 prevented HFD-evoked hypertension, reduced HFD-evoked polarization of adipose tissue macrophages toward the M1-like pro-inflammatory type and reduced HFD-evoked nociceptive hypersensitivity, but had no effect on weight gain.
CONCLUSIONS: CB2 agonists may fortify CB2-mediated anti-obesity signaling without the risk of anti-CB1-mediated depression that caused the failure of rimonabant.

: http://publica.fraunhofer.de/documents/N-382162.html