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

Toyozaki, M; Osaka, Mizuko; Kondo, Kazuo; Yoshida, Masayuki

doi:10.5650/jos.62.201

Cited by 4 publications

(6 citation statements)

References 20 publications

(15 reference statements)

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“…This confirms a previous report in rats showing DPP-4 in the mesenteric lymph duct [22]. The origin of lymph DPP-4 is probably the lymph epithelium, which previously has been shown to express DPP-4 [22]. The lymph DPP-4 activity was biologically active as evident from comparing intact GLP-1 levels in the lymph with versus without DPP-4 inhibition; it was found that DPP-4 inhibition substantially raised lymph intact GLP-1 after glucose and fat instillation.…”

Section: Discussionsupporting

confidence: 93%

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GLP-1 released to the mesenteric lymph duct in mice: Effects of glucose and fat

Ohlsson

Kohan

Tso

et al. 2014

Regulatory Peptides

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Using a newly developed in vivo model measuring glucagon-like peptide-1 (GLP-1) in gut lymphatics in mice, we quantified GLP-1 secretion in vivo after glucose versus fat ingestion with and without concomitant DPP-4 inhibition. The mesenteric lymphatic duct was cannulated in anesthetized C57BL6/J mice and lymph was collected in 30 min intervals. Glucose or fat emulsion (IntralipidR) (0.03, 0.1 or 0.3 kcal) with or without DPP-4-inhibition (NVP DPP728; 10 μmol/kg) was administered by gastric gavage. Basal intact GLP-1 levels were 0.37 ± 0.04 pmol/l (n = 61) in lymph compared to 0.07 ± 0.03 in plasma (n = 6; P = 0.04) and basal DPP-4 activity was 4.7 ± 0.3 pmol/min/μl in lymph (n = 23) compared to 22.3 ± 0.9 pmol/min/μl in plasma (n = 8; P < 0.001). Lymph flow increased from 1.2 ± 0.1 μl/min to 2.3 ± 02 μl/min at 30 min after glucose and fat administration, with no difference between type of challenge or dose (n = 81). Lymph GLP-1 levels increased calorie-dependently after both glucose and fat but with different time courses in that glucose induced a transient increase which had returned to baseline after 90 min whereas the lipid induced a sustained increase which was still elevated above baseline after 210 min. Lymph GLP-1 appearance during 210 min was two to three-fold higher after glucose (7.4 ± 2.3 fmol at 0.3 kcal) than after isocaloric fat (2.9 ± 0.8 fmol at 0.3 kcal; P < 0.001). The slope between caloric load and lymph GLP-1 appearance was, however, identical after glucose and fat. We conclude that lymph GLP-1 is higher than plasma GLP-1 whereas lymph DPP-4 activity is lower than plasma DPP-4 activity and that both glucose and fat clearly stimulate GLP-1 secretion calorie-dependently in vivo but with different time courses.

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Section: Discussionsupporting

confidence: 93%

“…We found that there is indeed DPP-4 activity in the lymph, but it is only approximately 30% of that in the peripheral plasma. This confirms a previous report in rats showing DPP-4 in the mesenteric lymph duct [22]. The origin of lymph DPP-4 is probably the lymph epithelium, which previously has been shown to express DPP-4 [22].…”

Section: Discussionsupporting

confidence: 92%

GLP-1 released to the mesenteric lymph duct in mice: Effects of glucose and fat

Ohlsson

Kohan

Tso

et al. 2014

Regulatory Peptides

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“…Therefore, peptides and other macromolecules are sequestered in the lymphatic system before entering the circulation (58). Additionally, bioactive peptides sustain a higher half-life given that proteolytic enzymes, such as dipeptidyl peptidase IV, are found at lower concentrations than in sera (65). Using rats with mesenteric lymph fistulas, it was demonstrated that the mesenteric lymph contains gastric inhibitory polypeptide, secreted from EECs, at significantly higher concentrations and of a longer half-life than that found in the circulation (52).…”

Section: Discussionmentioning

confidence: 99%

Feeding-dependent activation of enteric cells and sensory neurons by lymphatic fluid: evidence for a neurolymphocrine system

Poole

Lee

Tso

et al. 2014

American Journal of Physiology-Gastrointestinal and Liver Physi

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GW. 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 -G698, 2014. First published February 27, 2014 doi:10.1152/ajpgi.00433.2013.-Lymphatic fluid is a plasma filtrate that can be viewed as having biological activity through the passive accumulation of molecules from the interstitial fluid. The possibility that lymphatic fluid is part of an active self-contained signaling process that parallels the endocrine system, through the activation of G-protein coupled receptors (GPCR), has remained unexplored. We show that the GPCR lysophosphatidic acid 5 (LPA5) is found in sensory nerve fibers expressing calcitonin gene-related peptide (CGRP) that innervate the lumen of lymphatic lacteals and enteric nerves. Using LPA5 as a model for nutrient-responsive GPCRs present on sensory nerves, we demonstrate that dietary protein hydrolysate (peptone) can induce c-Fos expression in enterocytes and nerves that express LPA5. Mesenteric lymphatic fluid (MLF) mobilizes intracellular calcium in cell models expressing LPA5 upon feeding in a time-and dose-dependent manner. Primary cultured neurons of the dorsal root ganglia expressing CGRP are activated by MLF, which is enhanced upon LPA5 overexpression. Activation is independent of the known LPA5 agonists, lysophosphatidic acid and farnesyl pyrophosphate. These data bring forth a pathway for the direct stimulation of sensory nerves by luminal contents and interstitial fluid. Thus, by activating LPA5 on sensory nerves, MLF provides a means for known and yet to be identified constituents of the interstitial fluid to act as signals to comprise a "neurolymphocrine" system. G protein-coupled receptor; intestine; lacteal; lysophosphatidic acid 5; nutrient sensing NUTRIENT SENSING IS INCREASINGLY being recognized as affecting the etiology of diseases resulting from obesity, inflammation, dysregulation of intracellular metabolism, and modification of behavior such as food intake.

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“…In the blood these incretins have a half-life of only 2–3 min. However, DPP-4 activity is relatively low in the lymph, allowing more distant delivery of these incretins at higher concentrations than in the blood (627, 790, 1077, 1177). A functional implication is that lymphatic vessels may serve as an important route for certain endocrine signals, such as incretins.…”

Section: Organization and Anatomy Of The Lymphatic Systemmentioning

confidence: 99%

Lymphatic Vessel Network Structure and Physiology

Breslin

Yang

Scallan

et al. 2018

Comprehensive Physiology

274

258

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The lymphatic system is comprised of a network of vessels interrelated with lymphoid tissue, which has the holistic function to maintain the local physiologic environment for every cell in all tissues of the body. The lymphatic system maintains extracellular fluid homeostasis favorable for optimal tissue function, removing substances that arise due to metabolism or cell death, and optimizing immunity against bacteria, viruses, parasites, and other antigens. This article provides a comprehensive review of important findings over the past century along with recent advances in the understanding of the anatomy and physiology of lymphatic vessels, including tissue/organ specificity, development, mechanisms of lymph formation and transport, lymphangiogenesis, and the roles of lymphatics in disease.

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

Cited by 4 publications

References 20 publications

GLP-1 released to the mesenteric lymph duct in mice: Effects of glucose and fat

GLP-1 released to the mesenteric lymph duct in mice: Effects of glucose and fat

Feeding-dependent activation of enteric cells and sensory neurons by lymphatic fluid: evidence for a neurolymphocrine system

Lymphatic Vessel Network Structure and Physiology

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