Brain Nutrient Sensing: A Unifying Framework

Figures

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  Figure 1. The nutrient sensing niche. Brain nutrient sensing occurs within a unifying nutrient-sensing niche which includes: 1) vascular and barrier cells of the blood-brain barrier (BBB) and in circumventricular organs (CVOs), which modulate the rate and range of nutrient access to the niche, 2) non-neuronal cells, which support circuit activity, mediate structural remodelling within the niche and have direct nutrient-sensing capacity, 3) nutrient-sensing afferents, and 4) nutrient-sensing neurons, which produce the electrical, neurotransmitter and neuropeptide signals modulating the activity of downstream effector circuits. FA: fatty acids, Glc: glucose, AA: amino acids.

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  Figure 2. Brain nutrient detection: Sensing versus fuelling. Nutrients recruit energy-dependent intracellular mechanisms to change the functional output of nutrient-sensing cells. Energy-dependant sensing mechanisms also provide neuromodulatory inputs, changing the consequences of other nutrient-sensing events in the nutrient-sensing niche. Energy-independent sensing pathways alter the functional output of nutrient-sensing cells independently of fuel availability. MCT: monocarboxylate transporter

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  Figure 3. Brain integration of nutrient-sensing inputs. Circulating meal-related signals and ascending nutrient-sensing afferents alter the neurophysiolgical activity of distributed populations of brain nutrient-sensing neurons, which regulate downstream neural circuits for behavioural and metabolic feedback controls. Detection of different meal-related inputs can be integrated at the cell autonomous level within nutrient-sensing neurons sensitive to different sensing modalities, or at the circuit level in neuronal populations receiving convergent nutrient-sensing inputs. Future study is critical to identify and characterize parallel and distinct nutrient-sensing inputs, and to understand how activity across circuits may be integrated to generate a unified control of behavioural and metabolic circuits for short- and long-term nutrient homeostasis.