The Durk Pearson & Sandy Shaw®
Life Extension NewsTM
Volume 18 No. 3 • July 2015

Dysregulation of Metabolism and Immune Function in Obesity Points to Novel Therapeutic Approaches Involving the Cholinergic Antiinflammatory Pathway

A 2012 review paper6 describes how “cholinergic mechanisms within the inflammatory reflex have, in the past 2 years, been implicated in attenuating obesity-related inflammation and metabolic complications. This knowledge has led to the exploration of novel therapeutic approaches in the treatment of obesity-related disorders.”

As the authors note, “[d]ecreased vagus nerve activity in the context of obesity has been reported. Selective cholinergic activation within the efferent vagus nerve-mediated arm of the inflammatory reflex can suppress obesity-associated inflammation and reverse metabolic complications. These findings raise the intriguing possibility that dysregulation of vagus nerve-mediated signalling might contribute to the pathogenesis of obesity and its related comorbidities.” Later in the paper, the authors describe how the cholinergic antiinflammatory pathway suppresses the production of major inflammatory cytokines such as TNF-alpha, via the administration of alpha-7-nicotinic acetylcholine receptor agonists (which includes the nutrient choline6B) or a centrally-acting acetylcholinesterase inhibitor, such as galantamine. [See “Maintain your Brain the Durk Pearson & Sandy Shaw Way” in the May 2004 issue of Life Enhancement.] The authors describe how galantamine treatment of mice with high-fat induced obesity and hyperglycemia had reduced plasma levels of IL-6, CCL2, leptin, and resistin levels to levels detected in lean control mice.7 They further explain that cholinergic signaling, such as that of alpha-7-nicotinic acetylcholine receptor agonists in brain regions such as the lateral hypothalamus, implicated as part of the brain’s control system for appetite and feeding behavior, can suppress food intake.

6. Pavlov and Tracey. The vagus nerve and the inflammatory reflex—linking immunity and metabolism. Nat Rev Endocrinol. 8(12):743-54 (2012).
6B. Mike, Castro, Albuquerque. Choline and acetylcholine have similar kinetic properties of activation and desensitization on the alpha7 nicotinic receptors in rat hippocampal neurons. Brain Res. 882:155-68 (2000).
7. Satapathy, Ochani, et al. Galantamine alleviates inflammation and other obesity-associated complications in high-fat diet-fed mice. Mol Med. 17(7-8): 599-606 (2011).

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