Advanced neurobiological tools to interrogate metabolism

Engineered neurobiological tools for the manipulation of cellular activity, such as chemogenetics and optogenetics, have become a cornerstone of modern neuroscience research. These tools are invaluable for the interrogation of the central control of metabolism as they provide a direct means to establish a causal relationship between brain activity and biological processes at the cellular, tissue and organismal levels. The utility of these methods has grown substantially due to advances in cellular-targeting strategies, alongside improvements in the resolution and potency of such tools. Furthermore, the potential to recapitulate endogenous cellular signalling has been enriched by insights into the molecular signatures and activity dynamics of discrete brain cell types. However, each modulatory tool has a specific set of advantages and limitations; therefore, tool selection and suitability are of paramount importance to optimally interrogate the cellular and circuit-based underpinnings of metabolic outcomes within the organism. Here, we describe the key principles and uses of engineered neurobiological tools. We also highlight inspiring applications and outline critical considerations to be made when using these tools within the field of metabolism research. We contend that the appropriate application of these biotechnological advances will enable the delineation of the central circuitry regulating systemic metabolism with unprecedented potential. This Review discusses the key principles and uses of engineered neurobiological tools, such as optogenetics and chemogenetics. The authors discuss examples of their use in the metabolism field and highlight important points to consider when choosing an experimental technique. Neurobiological tools facilitate the probing of the interaction between discrete cell populations of the brain and systemic metabolism with unprecedented potential.Chemogenetic and optogenetic tools have different properties, which enables their complementary use to optimize the testing of the necessity and sufficiency of metabolic neural circuitry.The relative advantages and drawbacks of chemogenetic and optogenetic tools are important considerations as they dictate the ideal experimental conditions under which these tools should be used.The delineation and subsequent dissection of the complex neural circuitry underlying metabolism can leverage novel translational elements and pharmacological strategies for the treatment of metabolic diseases.

Automated summary

Engineered neurobiological tools, such as chemogenetics and optogenetics, are essential for studying the central control of metabolism and establishing causal relationships between brain activity and biological processes. Advances in cellular-targeting strategies and tool potency have improved their utility, and insights into brain cell types have enriched their potential to mimic endogenous signaling. However, tool selection and suitability are crucial for investigating metabolic outcomes, as each tool has specific advantages and limitations.