Research Description
Our laboratory has been characterizing how dietary nutrients (before they are metabolized) can be signals that cause changes in gene regulation and/or the release of bioactive molecules from peripheral tissues and nerves. We discovered specific receptors on sensory neurons that are stimulated by nutrients, hormones, and unique molecules present in lymphatic fluid. We are investigating if these neurons are part of a system whereby dietary molecules (and also molecules from peripheral tissues) can activate local neurons that stimulate tissues like the pancreas, spinal nerves and/or the brain. This system provides a new pathway for the regulation of central nervous system activity, metabolism, and behavior in response to biologically active molecules and nutrients, and expands our concept of the gut-brain axis.
Publications
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Heller RS, and Aponte GW. 1995. Intra islet regulation of hormone secretion by glucagon-like peptide-1 (7-36) amide. Am J Physiol 269: G1-9.
Lee M, Hadi M, Hallden G, and Aponte GW. 2005. Peptide YY and neuropeptide Y induce expression, reduce adhesion, and enhance migration in small intestinal cells through the regulation of CD63, matrix metalloproteinase-3, and Cdc42 activity. J Biol Chem 280: 125-36.
Choi S, Lee M, Shiu AL, Yo SJ, and Aponte GW. 2007. Identification of a protein hydrolysate responsive G protein coupled receptor in enterocytes. Am J Physiol Gastrointest Liver Physiol 292: G98-G112.
Choi S, Lee M, Yo SJ, Shiu AL, Halldén G, and Aponte GW. 2007. GPR93 activation by protein hydrolysate induces CCK transcription and secretion in STC-1 cells. Am J Physiol Gastrointest Liver Physiol 292: G1366-1375.
Lee M, Choi S, Shiu AL, Yo SJ, and Aponte GW. 2009. P2Y5 is a G{alpha}i, G{alpha}12/13 G Protein Coupled Receptor Activated by Lysophosphatidic Acid that Reduces Intestinal Cell Adhesion. Am J Physiol Gastrointest Liver Physiol 297:641-654.
Poole DP, Lee M, Tso P, Bunnett NW, Yo SJ, Lieu T, Shiu A, Wang JC, Nomura DK, and Aponte GW. 2014. Feeding-dependent activation of enteric cells and sensory neurons by lymphatic fluid: evidence for a neurolymphocrine system. Am J Physiol Gastrointest Liver Physiol 306:G686-698.
Mayer F, Gunawan AL, Tso P, Aponte GW. 2020 Glucagon like peptide 1 and glucose-dependent insulinotropic polypeptide stimulate the release of substance P from TRPV1 and TRPA1 expressing sensory nerves. Am J Physiol Gastrointest Liver Physiol Jul 1;319(1):G23-G35.
A key discovery finds nutrient molecules that send message to the brain. Article featured in BREAKTHROUGHS magazine.
Recent Teaching
NUSCTX 10S : Introduction to Human Nutrition: Managing Life
NUSCTX 299: Nutritional Sciences and Toxicology Research
Nutrient stimulation of the gut-brain axis: 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.
