Research Expertise and Interest

health and nutrition, nutritional sciences, signaling between the gut and the brain, neuropeptides, G-protein coupled receptors

Research Description

The Aponte Lab has been characterizing how dietary nutrients (before they are metabolized and enter the body and are assimilated) can be signals that cause changes in gene regulation and/or the release of bioactive molecules from peripheral tissues and nerves. In his early work Gregory Aponte was the first to demonstrate that these nutrients could directly act as signaling molecules to induce the release of a hormone. This hormone, called peptide-YY, is synthesized in the intestine and released in response to the presence of dietary fat. Peptide-YY is known to affect pancreatic and intestinal functions and food intake behavior. Those studies led to the hypothesis that there were nutrient receptors that directly mediated hormone secretion from the guts that could act as environmental signal molecules. Aponte group discovered a receptor, LPA5, a member of a family of receptors called G-protein coupled receptors (GPCR), that is activated by digested proteins present in the intestine. This activation causes the release of cholecystokinin (CCK) from intestinal CCK cells that results in pancreatic release of digestive enzymes.  LPA5 was found both on cells of the intestine as well as sensory nerves that are in contact with the lymphatic fluid of the gut.  Aponte lab demonstrated that lymphatic fluid activated sensory neurons and elucidated a neurolymphocrine system. Gut lymphatic fluid contains dietary nutrients as well as peptide hormones like glucagon like peptide-1 (GLP-1), glucose-dependent insulinotropic polypeptide (GIP), as well as other nutrient responsive bioactive peptides, CCK, peptide-YY, and somatostatin. Until the discovery of the neurolymphocrine system the presence of these molecules of the lymph was not considered biologically significant. GLP-1 and GIP are incretins, defined as gut hormones that potentiate glucose-stimulated insulin secretion and function. Aponte lab showed that GLP-1 of the lymph induces the release of the neuropeptide substance P. One action of substance P is to enhance insulin secretion. Thus, a pathway of nutrient sensing for peripheral tissues, such as the pancreas, and the brain is present through the lymphatic system of the gut.

Currently, the Aponte lab is characterizing sensory nerve types (both by function and transcriptional analysis) that are stimulated by GLP-1 and GIP, as well as by other nutrient responsive bioactive peptides found in the lymphatic fluid, such as cholecystokinin, peptide-YY and somatostatin. This will allow for the functional grouping of gut-pancreas sensory nerve types that could be activated by incretins, and incretins found in the neurolymphocrine system. The lab is also investigating the role of mesenteric nerves in in the regulation of the neurolymphocrine system to help determine if the neurolymphocrine induces responses in the brain through vagal as well as spinal pathways.