Our past research identified nutrient-sensing cell populations in the brain that can detect changes in amino acid availability, in particular the branched-chain amino acid leucine. These are located both in the hypothalamus and the brainstem, and we found that they can modulate multiple effectors of energy intake (meal latency, meal number, meal size). We showed that these amino acid sensing cells are neurochemically heterogeneous, include POMC neurons, catecholaminergic neurons, Agrp neurons but also unidentified neuronal populations. They can affect feeding behaviour via multiple mechanisms that affect both the acute and the long-term activity of feeding-regulatory circuits. However, primary amino acid sensing mechanisms and downstream output to peripheral effectors of energy balance remain poorly characterized.
Dietary protein quantity and quality greatly impact metabolic health via evolutionary-conserved mechanisms that ensure avoidance of amino acid imbalanced food sources, promote hyperphagia when dietary protein density is low, and conversely produce satiety when dietary protein density is high. Growing evidence support the emerging concept of protein homeostasis in mammals, where protein intake is maintained within a tight range independently of energy intake to reach a target protein intake. The behavioural and neuroendocrine mechanisms underlying these adaptations are unclear. While peripheral factors are able to signal amino acid deficiency and abundance to the brain, the brain itself is exposed to and can detect changes in amino acid concentrations, and subsequently engages acute and chronic responses modulating feeding behaviour and food preferences.
Our current work focuses on the molecular and electrophysiological characterization of hypothalamic leucine-sensing neurons, and the identification of downstream neurocircuits modulating feeding behaviour and energy expenditure acutely and chronically.