Food contains macronutrients, namely carbohydrates, protein, and fat. A balanced intake of these macronutrients is essential for the well-being of organisms. Protein, a crucial nutrient, is comprised of essential amino acids (EAAs) and non-essential amino acids (NEAAs). EAAs are not produced by our bodies and must be acquired from external food sources, whereas NEAAs are synthesized by our bodies. As such, our bodies must have a system to meticulously monitor EAA levels and induce a specific appetite for EAAs or protein, ensuring the maintenance of proper EAA homeostasis. In our laboratory, we have recently identified and characterized specific populations of the gut cells and the brain cells responsible for detecting and responding to the deprivation (or absence) of EAAs in Drosophila (Kim et al., 2021 Nature) and are currently investigating how these cells selectively direct the intake of protein or EAAs and not necessarily sugar or fat. Furthermore, we aim to identify and characterize the molecules and cells that directly detect each EAAs in the gut, and respond to the presence of EAAs. We are extending the line of studies to rodents.

Another goal of our laboratory is to identify glucose sensors or glucose-sensing neurons, and characterize the physiological roles mediated by these molecules and cells. Glucose-sensing neurons respond to glucose or its metabolites, which act as signaling cues to regulate their neuronal activity. According to the glucostatic hypothesis proposed in 1953, feeding and related behaviors are regulated by neurons in the brain that sense changes in glucose levels in the blood (Mayer, 1953 NEJM). Despite the discovery of glucose-sensing neurons in the hypothalamus through electrophysiological methods more than ten years later (Oomura et al., 1964 Science), the physiological role of these neurons remained unclear until recently, when a population of DH44-expressing glucose-excited neurons in the Drosophila brain, which our laboratory identified and characterized, were determined to function as an internal nutrient sensor to mediate the intake of sugar in animals (Parton et al., 2007 Nature; Levin, 2007 Cell Metabolism; Dus et al., 2015 Neuron; Oh et al., 2021 Neuron). In addition to the glucose-sensing neurons that mediate sugar consumption, we identified a pair of glucose-excited neurons that promote the release of insulin and, at the same time, inhibit the release of glucagon during a period of hyperglycemia, thereby maintaining glucose homeostasis (Oh et al., 2019 Nature).

There are a large number of glucose-excited and glucose-inhibited neurons in animals. Our laboratory would like to understand distinct physiological functions mediated by different populations of glucose-sensing neurons in the brain and enteric system.