Using the lymphatics to study nutrient absorption and the secretion of gastrointestinal hormones

Abstract

The lymph fistula rat model has traditionally been used to study the intestinal absorption of nutrients, especially lipids, but recently this model has also been used for studying the secretion of incretin hormones by the small intestine. The small intestine is not only responsible for the digestion and transport of dietary triacylglycerol, through the formation of chylomicrons, but it also secretes the incretin hormones glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1 (GLP-1) from enteroendocrine cells. Ultimately, both chylomicrons and incretins are found in lymph. Advantages of the lymph fistula rat model in studying chylomicron and incretin secretion are numerous and include: 1) the concentrations of incretin hormones are higher in lymph than in peripheral or portal plasma; 2) there is reduced degradation of incretin hormones by DPP-IV in the lymph compartment; 3) less dilution by the circulating fluid; 4) this model allows the continuous collection of lymph from conscious animals, eliminating any potential side effects on lymph flow and gastrointestinal function due to anesthesia; and finally, and perhaps most importantly, 5) the concentration in the intestinal lymph provides a physiologically accurate representation of the hormonal milieu within the intestinal mucosa where incretins may interact with enteroendocrine and/or dendritic cells and signal through the enteric or autonomic neurons. The importance of GIP and GLP-1 in health and disease is becoming more apparent, especially as the prevalence of type 2 diabetes and other metabolic disorders increases. This review focuses on the use of the lymph fistula rat as a model to study the secretion of incretins, as well as dietary lipid.

High Fat and High Cholesterol Diet Induces DPP-IV Activity in Intestinal Lymph

“…Our findings revealed an important role for intestinal lymph in systemic up-regulation of DPP-IV after rats received an HFHC diet. It was previously reported that under non-diabetic conditions, DPP-IV activity in intestinal lymph is lower than that in plasma 14 , which helps to maintain the plasma concentration of the incretin family of bioactive peptides, including GLP-1 and -2 15 . Therefore, up-regulation of DPP-IV in type 2 diabetes reduces the plasma levels of GLP-1 and -2, which may contribute to development of the disease.…”

Impairments in the intrinsic contractility of mesenteric collecting lymphatics in a rat model of metabolic syndrome

“…High fructose diet feeding, in addition to high-fat diet feeding, increases gut permeability to dietary endotoxin (32,54). Dietary endotoxin readily associates with chylomicrons, which are primarily passed through the mesenteric lymphatics (66) along with many other gut peptides and hormones (44), suggesting that the primary trafficking of LPS is through lymphatic vessels (36,62,70,72). Lymphatic endothelial cells (42,52) and lymphatic muscle cells (unpublished observations) express multiple Toll-like receptors, are functionally responsive to LPS, and could potentially modulate their own inflam- matory activation (58).…”

“…THE LYMPHATIC SYSTEM is involved in immune cell trafficking (6,55), antigen transport and presentation (32), fluid and macromolecular homeostasis, oncotic balance, passage of gut satiety signals (44), and transport of dietary lipids (11,74). Proper lymphatic function requires an effective transport of lymph through the lymphatic system and is driven by intrinsic contractility and extrinsic motive forces, failures of which can lead to edema.…”

Apolipoprotein A-IV: a protein intimately involved in metabolism

“…2 , mice are fi tted with lymphatic cannulas for the collection of lymph secreted from the small intestine, and with a gastric or duodenal cannula for the delivery of lipid emulsion directly into the stomach or intestinal lumen. This conscious mouse model allows direct quantitation of the output of dietary (infused) lipids into the intestinal lymph, the amount of lipid remaining in the lumen (not yet taken up by enterocytes), and the amount taken up by enterocytes but not yet transported into lymph as chylomicrons ( 69,70 ). The key advantages of this model are that: 1 ) the animal is conscious, enabling the effi cient and rapid packaging and secretion of chylomicrons during active intestinal lipid infusion; 2 ) lymph can be continuously sampled over the course of many hours, both during and after lipid infusion; 3 ) animals can act as their own controls, thus reducing the number of animals needed for study; and 4 ) lymph is sampled prior to its entry into the blood, so there is no confounding effect of peripheral metabolism to obscure the results.…”