Protein-induced satiation and the calcium-sensing receptor

Abstract

Obesity is a major global health issue. High-protein diets have been shown to be associated with weight loss and satiety. The precise mechanism by which protein-rich diets promote weight loss remains unclear. Evidence suggests amino acids, formed as a consequence of protein digestion, are sensed by specific receptors on L-cells in the gastrointestinal (GI) tract. These L-cells respond by secreting gut hormones that subsequently induce satiety. In recent years, the calcium-sensing receptor has been identified in several cells of the GI tract, including L-cells, and suggested to sense specific amino acids. This review evaluates the evidence for protein-rich diets in inducing weight loss and how the calcium-sensing receptor may be implicated in this phenomenon. Commandeering the mechanisms by which elements of a protein-rich diet suppress appetite may provide another successful avenue for developing anti-obesity drugs.

Keywords: amino acids; energy regulation; glucagon-like-peptide-1; obesity therapy; peptide YY.

Figure 1

Gut–brain axis: consequence of amino acid sensing by receptors on the EEC. Notes: Following sensing of amino acids by receptors on the EEC, peptides such as GLP-1 and PYY are secreted from the EEC and regulate food intake by binding to their respective receptors. PYY binds to Y2R located on the vagus nerve fiber terminals, which signals to the brain stem and eventually the hypothalamus. GLP-1 can pass through the blood and act directly at GLP-1 receptors in the hypothalamus and exert its effects on satiety. The hypothalamus has a collection of nuclei (not shown in Figure 1); the ARC is a collection of neurons in the mediobasal hypothalamus, and is thought to be implicated in the control of food intake. The ARC contains two populations of neurons with opposing effect on food intake. The agouti-related peptide/neuropeptide Y neurons stimulate food intake, whereas pro-opiomelanocortin neurons suppress appetite. The ARC also sends numerous projections to both extra- and intra-hypothalamic regions responsible for energy homeostasis, including the paraventricular nucleus. Further connections are formed between these populations of neurons and higher brain centers. Abbreviations: ARC, arcuate nucleus; CaSR, calcium-sensing receptor; EEC, enteroendocrine cells; GLP-1, glucagon-like peptide-1; GPRC6A, G-protein-coupled receptor family C group 6-member A; PYY, peptide tyrosine tyrosine; T1R, taste receptor 1; Y2R, Y2 receptors.