Abstract
Obesity and obesity-associated disorders have become world-wide epidemics, substantially increasing the risk of debilitating morbidity and mortality. A characteristic feature of these disorders, which include the metabolic syndrome (MetS) and type 2 diabetes, is chronic low-grade inflammation stemming from metabolic and immune dysregulation. Inflammation in the CNS (neuroinflammation) and cognitive impairment have also been associated with obesity-driven disorders. The nervous system has a documented role in the regulation of metabolic homeostasis and immune function, and recent studies have indicated the important role of vagus nerve and brain cholinergic signaling in this context. In this review, we outline relevant aspects of this regulation with a specific focus on obesity-associated conditions. We outline accumulating preclinical evidence for the therapeutic efficacy of cholinergic stimulation in alleviating obesity-associated inflammation, neuroinflammation, and metabolic derangements. Recently demonstrated beneficial effects of galantamine, a centrally acting cholinergic drug and cognitive enhancer, in patients with MetS are also summarized. These studies provide a rationale for further therapeutic developments using pharmacological and bioelectronic cholinergic modulation for clinical benefit in obesity-associated disorders.
Highlights
Obesity and obesity-related disorders have become prevalent conditions in our modern society, impacting over 1 billion people worldwide (Zimmet et al, 2001; Grundy, 2008; Aguilar et al, 2015; Kim et al, 2019)
We briefly summarize the role of brain and the vagus nerve cholinergic signaling in the regulation of metabolic homeostasis and the role of the vagus nervebased inflammatory reflex in controlling inflammation
Vagus nerve cholinergic signaling within the inflammatory reflex has an important regulatory role in the crosstalk between immune and metabolic alterations in obesity-driven disorders
Summary
Obesity and obesity-related disorders have become prevalent conditions in our modern society, impacting over 1 billion people worldwide (Zimmet et al, 2001; Grundy, 2008; Aguilar et al, 2015; Kim et al, 2019). Cholinergic compounds, including α7nAChR agonists and centrally acting acetylcholinesterase inhibitors (AChE), have been shown to alleviate inflammation and metabolic derangements in obesity and MetS (Pavlov and Tracey, 2012). Recent studies have provided important new insights into the role of the brain in the control of peripheral metabolic function and in the context of obesitydriven disorders, including type 2 diabetes.
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