Neuromodulation of metabolic functions: from pharmaceuticals to bioelectronics to biocircuits

Figures

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  Fig. 1. Target organs and progression of neuromodulation technologies to control metabolic functions. Neuromodulation can be categorized based on the peripheral target innervated by the circuit or nerve stimulated. a. Target organs that regulate metabolism are innervated by afferent and efferent fibers that release neurotransmitters or paracrine signals which modulate the organ’s function and greatly impact local and systemic metabolisms. b. Pharmaceutical interventions for T1D. Blood glucose level is self-measured, and insulin is injected via syringe multiple times daily. Closed-loop advanced drug delivery systems greatly improve disease management outcomes and patients’ life quality. c. DBS and VNS systems for bioelectronic medicine require implanted stimulators that generate electrical pulses. They are then connected by wires to microelectrodes implanted in the brain or on the vagus nerve. d. Using a hydrogel-based micro-TENN as scaffold [53], neuronal networks can be rationally designed and transplanted to innervate and/or replace living tissues. An autologous β-cell biocircuit concept consists of ACh releasing neurons inside a micro-TENN with directed innervation into vascularized,…

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  Fig. 2. Neuroendocrine and neurometabolic circuitry regulation of metabolic functions. Both afferent and efferent pathways regulate energy balance through hormones and direct neural circuits. Ghrelin, insulin and leptin are the primary hormones that mediate the sensation of satiety and hunger by activating various populations of neurons in different regions of the brain. Autonomic innervations of metabolic organs are also depicted. SNS efferent fibers control hepatic and adipocyte metabolic pathways. Vagal afferents and efferent continuously monitor and regulate systemic metabolism. Cellular metabolism, including the production and release of cytokines from the spleen, responds to the sympathetic and parasympathetic convergences in the celiac ganglion. Inset, the NPY/AgRP and POMC neurons in the ARC of the hypothalamus inversely respond to these hormones and modulate the activation of the PVN neurons that in turn regulate feeding behavior and metabolic functions. Deep brain stimulation of POMC neurons ameliorates symptoms of diabetes in rat models, and therefore may provide a therapeutic avenue for neuromodulatory treatment of metabolic diseases. Image courtesy of Anthony S. Baker and…