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

Area of Science:

• Immunology
• Metabolic Syndrome
• Neuroscience

Background:

• Cannabinoid-1 receptor (CB1) signaling promotes food intake and adipocyte growth, contributing to obesity.
• Cannabinoid-2 receptor (CB2) may counteract obesity by modulating immune cells involved in metabolic syndrome.
• Age-related immune and endocannabinoid system changes can disrupt the balance of cannabimimetic signaling.

Purpose of the Study:

• To investigate the role of CB2 in age-associated obesity.
• To analyze the effects of CB2 deficiency and CB2 agonist treatment on metabolic, cardiovascular, immune, and neuronal functions.

Main Methods:

• Analysis of metabolic, cardiovascular, immune, and neuronal functions in aged CB2(-/-) and control mice on a standard diet.
• Assessment of the CB2 agonist HU308 effects in mice on a high-fat diet (HFD).

Main Results:

• CB2(-/-) mice exhibited obesity, visceral fat hypertrophy, pro-inflammatory immune cell polarization, hypertension, and increased mortality.
• CB2(-/-) mice showed enhanced paw inflammation and premature loss of sensory neuron responsiveness.
• HU308 treatment prevented HFD-evoked hypertension, reduced pro-inflammatory macrophage polarization, and mitigated nociceptive hypersensitivity, but did not affect weight gain.

Conclusions:

• CB2 agonists may enhance anti-obesity effects mediated by CB2 signaling.
• CB2-targeted therapies could avoid the adverse effects associated with CB1 antagonists like rimonabant.