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Protein Kinase D2 drives chylomicron‐mediated lipid transport in the intestine and promotes obesity

Lipids are the most energy‐dense components of the diet, and their overconsumption promotes obesity and diabetes. Dietary fat content has been linked to the lipid processing activity by the intestine and its overall capacity to absorb triglycerides (TG). However, the signaling cascades driving intes...

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Autores principales: Trujillo‐Viera, Jonathan, El‐Merahbi, Rabih, Schmidt, Vanessa, Karwen, Till, Loza‐Valdes, Angel, Strohmeyer, Akim, Reuter, Saskia, Noh, Minhee, Wit, Magdalena, Hawro, Izabela, Mocek, Sabine, Fey, Christina, Mayer, Alexander E, Löffler, Mona C, Wilhelmi, Ilka, Metzger, Marco, Ishikawa, Eri, Yamasaki, Sho, Rau, Monika, Geier, Andreas, Hankir, Mohammed, Seyfried, Florian, Klingenspor, Martin, Sumara, Grzegorz
Formato: Online Artículo Texto
Lenguaje:English
Publicado: John Wiley and Sons Inc. 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8103097/
https://www.ncbi.nlm.nih.gov/pubmed/33949105
http://dx.doi.org/10.15252/emmm.202013548
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author Trujillo‐Viera, Jonathan
El‐Merahbi, Rabih
Schmidt, Vanessa
Karwen, Till
Loza‐Valdes, Angel
Strohmeyer, Akim
Reuter, Saskia
Noh, Minhee
Wit, Magdalena
Hawro, Izabela
Mocek, Sabine
Fey, Christina
Mayer, Alexander E
Löffler, Mona C
Wilhelmi, Ilka
Metzger, Marco
Ishikawa, Eri
Yamasaki, Sho
Rau, Monika
Geier, Andreas
Hankir, Mohammed
Seyfried, Florian
Klingenspor, Martin
Sumara, Grzegorz
author_facet Trujillo‐Viera, Jonathan
El‐Merahbi, Rabih
Schmidt, Vanessa
Karwen, Till
Loza‐Valdes, Angel
Strohmeyer, Akim
Reuter, Saskia
Noh, Minhee
Wit, Magdalena
Hawro, Izabela
Mocek, Sabine
Fey, Christina
Mayer, Alexander E
Löffler, Mona C
Wilhelmi, Ilka
Metzger, Marco
Ishikawa, Eri
Yamasaki, Sho
Rau, Monika
Geier, Andreas
Hankir, Mohammed
Seyfried, Florian
Klingenspor, Martin
Sumara, Grzegorz
author_sort Trujillo‐Viera, Jonathan
collection PubMed
description Lipids are the most energy‐dense components of the diet, and their overconsumption promotes obesity and diabetes. Dietary fat content has been linked to the lipid processing activity by the intestine and its overall capacity to absorb triglycerides (TG). However, the signaling cascades driving intestinal lipid absorption in response to elevated dietary fat are largely unknown. Here, we describe an unexpected role of the protein kinase D2 (PKD2) in lipid homeostasis. We demonstrate that PKD2 activity promotes chylomicron‐mediated TG transfer in enterocytes. PKD2 increases chylomicron size to enhance the TG secretion on the basolateral side of the mouse and human enterocytes, which is associated with decreased abundance of APOA4. PKD2 activation in intestine also correlates positively with circulating TG in obese human patients. Importantly, deletion, inactivation, or inhibition of PKD2 ameliorates high‐fat diet‐induced obesity and diabetes and improves gut microbiota profile in mice. Taken together, our findings suggest that PKD2 represents a key signaling node promoting dietary fat absorption and may serve as an attractive target for the treatment of obesity.
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spelling pubmed-81030972021-05-10 Protein Kinase D2 drives chylomicron‐mediated lipid transport in the intestine and promotes obesity Trujillo‐Viera, Jonathan El‐Merahbi, Rabih Schmidt, Vanessa Karwen, Till Loza‐Valdes, Angel Strohmeyer, Akim Reuter, Saskia Noh, Minhee Wit, Magdalena Hawro, Izabela Mocek, Sabine Fey, Christina Mayer, Alexander E Löffler, Mona C Wilhelmi, Ilka Metzger, Marco Ishikawa, Eri Yamasaki, Sho Rau, Monika Geier, Andreas Hankir, Mohammed Seyfried, Florian Klingenspor, Martin Sumara, Grzegorz EMBO Mol Med Articles Lipids are the most energy‐dense components of the diet, and their overconsumption promotes obesity and diabetes. Dietary fat content has been linked to the lipid processing activity by the intestine and its overall capacity to absorb triglycerides (TG). However, the signaling cascades driving intestinal lipid absorption in response to elevated dietary fat are largely unknown. Here, we describe an unexpected role of the protein kinase D2 (PKD2) in lipid homeostasis. We demonstrate that PKD2 activity promotes chylomicron‐mediated TG transfer in enterocytes. PKD2 increases chylomicron size to enhance the TG secretion on the basolateral side of the mouse and human enterocytes, which is associated with decreased abundance of APOA4. PKD2 activation in intestine also correlates positively with circulating TG in obese human patients. Importantly, deletion, inactivation, or inhibition of PKD2 ameliorates high‐fat diet‐induced obesity and diabetes and improves gut microbiota profile in mice. Taken together, our findings suggest that PKD2 represents a key signaling node promoting dietary fat absorption and may serve as an attractive target for the treatment of obesity. John Wiley and Sons Inc. 2021-05-05 2021-05-07 /pmc/articles/PMC8103097/ /pubmed/33949105 http://dx.doi.org/10.15252/emmm.202013548 Text en © 2021 The Authors. Published under the terms of the CC BY 4.0 license https://creativecommons.org/licenses/by/4.0/This is an open access article under the terms of the http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
spellingShingle Articles
Trujillo‐Viera, Jonathan
El‐Merahbi, Rabih
Schmidt, Vanessa
Karwen, Till
Loza‐Valdes, Angel
Strohmeyer, Akim
Reuter, Saskia
Noh, Minhee
Wit, Magdalena
Hawro, Izabela
Mocek, Sabine
Fey, Christina
Mayer, Alexander E
Löffler, Mona C
Wilhelmi, Ilka
Metzger, Marco
Ishikawa, Eri
Yamasaki, Sho
Rau, Monika
Geier, Andreas
Hankir, Mohammed
Seyfried, Florian
Klingenspor, Martin
Sumara, Grzegorz
Protein Kinase D2 drives chylomicron‐mediated lipid transport in the intestine and promotes obesity
title Protein Kinase D2 drives chylomicron‐mediated lipid transport in the intestine and promotes obesity
title_full Protein Kinase D2 drives chylomicron‐mediated lipid transport in the intestine and promotes obesity
title_fullStr Protein Kinase D2 drives chylomicron‐mediated lipid transport in the intestine and promotes obesity
title_full_unstemmed Protein Kinase D2 drives chylomicron‐mediated lipid transport in the intestine and promotes obesity
title_short Protein Kinase D2 drives chylomicron‐mediated lipid transport in the intestine and promotes obesity
title_sort protein kinase d2 drives chylomicron‐mediated lipid transport in the intestine and promotes obesity
topic Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8103097/
https://www.ncbi.nlm.nih.gov/pubmed/33949105
http://dx.doi.org/10.15252/emmm.202013548
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