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Free Fatty Acid-Induced Peptide YY Expression Is Dependent on TG Synthesis Rate and Xbp1 Splicing

Gut-derived satiety hormones provide negative feedback to suppress food intake and maintain metabolic function in peripheral tissues. Despite the wealth of knowledge of the systemic effects of these hormones, very little is known concerning the mechanisms by which nutrients, such as dietary fats, ca...

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Autores principales: Paton, Chad M., Son, Yura, Vaughan, Roger A., Cooper, Jamie A.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7247705/
https://www.ncbi.nlm.nih.gov/pubmed/32397573
http://dx.doi.org/10.3390/ijms21093368
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author Paton, Chad M.
Son, Yura
Vaughan, Roger A.
Cooper, Jamie A.
author_facet Paton, Chad M.
Son, Yura
Vaughan, Roger A.
Cooper, Jamie A.
author_sort Paton, Chad M.
collection PubMed
description Gut-derived satiety hormones provide negative feedback to suppress food intake and maintain metabolic function in peripheral tissues. Despite the wealth of knowledge of the systemic effects of these hormones, very little is known concerning the mechanisms by which nutrients, such as dietary fats, can promote the expression of genes involved in L-cell hormone production. We have tested the role of various dietary fats and found that after hydrolysis into free fatty acids (FFA’s), there is a differential response in the extent to which they induce PYY gene and protein production. The effect of FFA’s also seems to relate to triglyceride (TG) re-esterification rate, with MUFA re-esterifying faster with lower PYY production. We have also found that there are differences in potency of FFA’s based on their desaturation patterns in vitro. The potency effect of FFA’s is influenced by the rate of TG re-esterification, such that the longer FFA’s are in contact with L-cells, the more PYY they produce. We found that chronic consumption of high-fat diets enables the small intestine to re-esterify FFA’s into TG faster and earlier which resulted in a blunted postprandial PYY response. Lastly, we found that FFA’s induce X-box-binding protein-1 activation (Xbp1s) in L-cells and that adenoviral delivery of Xbp1s was sufficient to induce PYY gene expression. Taken together, the present work indicates that dietary fat can induce satiety, in part, prior to re-esterification. Chronic high-fat diet consumption increases the rate of re-esterification which diminishes satiety and may lead to increased food intake. Targeting intestinal TG synthesis may prove beneficial in restoring obesity-associated reductions in postprandial satiety.
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spelling pubmed-72477052020-06-10 Free Fatty Acid-Induced Peptide YY Expression Is Dependent on TG Synthesis Rate and Xbp1 Splicing Paton, Chad M. Son, Yura Vaughan, Roger A. Cooper, Jamie A. Int J Mol Sci Article Gut-derived satiety hormones provide negative feedback to suppress food intake and maintain metabolic function in peripheral tissues. Despite the wealth of knowledge of the systemic effects of these hormones, very little is known concerning the mechanisms by which nutrients, such as dietary fats, can promote the expression of genes involved in L-cell hormone production. We have tested the role of various dietary fats and found that after hydrolysis into free fatty acids (FFA’s), there is a differential response in the extent to which they induce PYY gene and protein production. The effect of FFA’s also seems to relate to triglyceride (TG) re-esterification rate, with MUFA re-esterifying faster with lower PYY production. We have also found that there are differences in potency of FFA’s based on their desaturation patterns in vitro. The potency effect of FFA’s is influenced by the rate of TG re-esterification, such that the longer FFA’s are in contact with L-cells, the more PYY they produce. We found that chronic consumption of high-fat diets enables the small intestine to re-esterify FFA’s into TG faster and earlier which resulted in a blunted postprandial PYY response. Lastly, we found that FFA’s induce X-box-binding protein-1 activation (Xbp1s) in L-cells and that adenoviral delivery of Xbp1s was sufficient to induce PYY gene expression. Taken together, the present work indicates that dietary fat can induce satiety, in part, prior to re-esterification. Chronic high-fat diet consumption increases the rate of re-esterification which diminishes satiety and may lead to increased food intake. Targeting intestinal TG synthesis may prove beneficial in restoring obesity-associated reductions in postprandial satiety. MDPI 2020-05-10 /pmc/articles/PMC7247705/ /pubmed/32397573 http://dx.doi.org/10.3390/ijms21093368 Text en © 2020 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Paton, Chad M.
Son, Yura
Vaughan, Roger A.
Cooper, Jamie A.
Free Fatty Acid-Induced Peptide YY Expression Is Dependent on TG Synthesis Rate and Xbp1 Splicing
title Free Fatty Acid-Induced Peptide YY Expression Is Dependent on TG Synthesis Rate and Xbp1 Splicing
title_full Free Fatty Acid-Induced Peptide YY Expression Is Dependent on TG Synthesis Rate and Xbp1 Splicing
title_fullStr Free Fatty Acid-Induced Peptide YY Expression Is Dependent on TG Synthesis Rate and Xbp1 Splicing
title_full_unstemmed Free Fatty Acid-Induced Peptide YY Expression Is Dependent on TG Synthesis Rate and Xbp1 Splicing
title_short Free Fatty Acid-Induced Peptide YY Expression Is Dependent on TG Synthesis Rate and Xbp1 Splicing
title_sort free fatty acid-induced peptide yy expression is dependent on tg synthesis rate and xbp1 splicing
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7247705/
https://www.ncbi.nlm.nih.gov/pubmed/32397573
http://dx.doi.org/10.3390/ijms21093368
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