Caspase-1 deficiency in mice reduces intestinal triglyceride absorption and hepatic triglyceride secretion[S]
Caspase-1 is known to activate the proinflammatory cytokines IL-1β and IL-18. Additionally, it can cleave other substrates, including proteins involved in metabolism. Recently, we showed that caspase-1 deficiency in mice strongly reduces high-fat diet-induced weight gain, at least partly caused by a...
| Main Authors: | , , , , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Elsevier
2013-02-01
|
| Series: | Journal of Lipid Research |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S0022227520428093 |
| id |
doaj-6e780bacf3b342febeb95866706387ee |
|---|---|
| record_format |
Article |
| collection |
DOAJ |
| language |
English |
| format |
Article |
| sources |
DOAJ |
| author |
Janna A. van Diepen Rinke Stienstra Irene O. C.M. Vroegrijk Sjoerd A.A. van den Berg Daniela Salvatori Guido J. Hooiveld Sander Kersten Cees J. Tack Mihai G. Netea Johannes W.A. Smit Leo A.B. Joosten Louis M. Havekes Ko Willems van Dijk Patrick C.N. Rensen |
| spellingShingle |
Janna A. van Diepen Rinke Stienstra Irene O. C.M. Vroegrijk Sjoerd A.A. van den Berg Daniela Salvatori Guido J. Hooiveld Sander Kersten Cees J. Tack Mihai G. Netea Johannes W.A. Smit Leo A.B. Joosten Louis M. Havekes Ko Willems van Dijk Patrick C.N. Rensen Caspase-1 deficiency in mice reduces intestinal triglyceride absorption and hepatic triglyceride secretion[S] Journal of Lipid Research caspase-1 chylomicron intestine lipid absorption liver triglyceride metabolism |
| author_facet |
Janna A. van Diepen Rinke Stienstra Irene O. C.M. Vroegrijk Sjoerd A.A. van den Berg Daniela Salvatori Guido J. Hooiveld Sander Kersten Cees J. Tack Mihai G. Netea Johannes W.A. Smit Leo A.B. Joosten Louis M. Havekes Ko Willems van Dijk Patrick C.N. Rensen |
| author_sort |
Janna A. van Diepen |
| title |
Caspase-1 deficiency in mice reduces intestinal triglyceride absorption and hepatic triglyceride secretion[S] |
| title_short |
Caspase-1 deficiency in mice reduces intestinal triglyceride absorption and hepatic triglyceride secretion[S] |
| title_full |
Caspase-1 deficiency in mice reduces intestinal triglyceride absorption and hepatic triglyceride secretion[S] |
| title_fullStr |
Caspase-1 deficiency in mice reduces intestinal triglyceride absorption and hepatic triglyceride secretion[S] |
| title_full_unstemmed |
Caspase-1 deficiency in mice reduces intestinal triglyceride absorption and hepatic triglyceride secretion[S] |
| title_sort |
caspase-1 deficiency in mice reduces intestinal triglyceride absorption and hepatic triglyceride secretion[s] |
| publisher |
Elsevier |
| series |
Journal of Lipid Research |
| issn |
0022-2275 |
| publishDate |
2013-02-01 |
| description |
Caspase-1 is known to activate the proinflammatory cytokines IL-1β and IL-18. Additionally, it can cleave other substrates, including proteins involved in metabolism. Recently, we showed that caspase-1 deficiency in mice strongly reduces high-fat diet-induced weight gain, at least partly caused by an increased energy production. Increased feces secretion by caspase-1-deficient mice suggests that lipid malabsorption possibly further reduces adipose tissue mass. In this study we investigated whether caspase-1 plays a role in triglyceride-(TG)-rich lipoprotein metabolism using caspase-1-deficient and wild-type mice. Caspase-1 deficiency reduced the postprandial TG response to an oral lipid load, whereas TG-derived fatty acid (FA) uptake by peripheral tissues was not affected, demonstrated by unaltered kinetics of [3H]TG-labeled very low-density lipoprotein (VLDL)-like emulsion particles. An oral gavage of [3H]TG-containing olive oil revealed that caspase-1 deficiency reduced TG absorption and subsequent uptake of TG-derived FA in liver, muscle, and adipose tissue. Similarly, despite an elevated hepatic TG content, caspase-1 deficiency reduced hepatic VLDL-TG production. Intestinal and hepatic gene expression analysis revealed that caspase-1 deficiency did not affect FA oxidation or FA uptake but rather reduced intracellular FA transport, thereby limiting lipid availability for the assembly and secretion of TG-rich lipoproteins. The current study reveals a novel function for caspase-1, or caspase-1-cleaved substrates, in controlling intestinal TG absorption and hepatic TG secretion. |
| topic |
caspase-1 chylomicron intestine lipid absorption liver triglyceride metabolism |
| url |
http://www.sciencedirect.com/science/article/pii/S0022227520428093 |
| work_keys_str_mv |
AT jannaavandiepen caspase1deficiencyinmicereducesintestinaltriglycerideabsorptionandhepatictriglyceridesecretions AT rinkestienstra caspase1deficiencyinmicereducesintestinaltriglycerideabsorptionandhepatictriglyceridesecretions AT ireneocmvroegrijk caspase1deficiencyinmicereducesintestinaltriglycerideabsorptionandhepatictriglyceridesecretions AT sjoerdaavandenberg caspase1deficiencyinmicereducesintestinaltriglycerideabsorptionandhepatictriglyceridesecretions AT danielasalvatori caspase1deficiencyinmicereducesintestinaltriglycerideabsorptionandhepatictriglyceridesecretions AT guidojhooiveld caspase1deficiencyinmicereducesintestinaltriglycerideabsorptionandhepatictriglyceridesecretions AT sanderkersten caspase1deficiencyinmicereducesintestinaltriglycerideabsorptionandhepatictriglyceridesecretions AT ceesjtack caspase1deficiencyinmicereducesintestinaltriglycerideabsorptionandhepatictriglyceridesecretions AT mihaignetea caspase1deficiencyinmicereducesintestinaltriglycerideabsorptionandhepatictriglyceridesecretions AT johanneswasmit caspase1deficiencyinmicereducesintestinaltriglycerideabsorptionandhepatictriglyceridesecretions AT leoabjoosten caspase1deficiencyinmicereducesintestinaltriglycerideabsorptionandhepatictriglyceridesecretions AT louismhavekes caspase1deficiencyinmicereducesintestinaltriglycerideabsorptionandhepatictriglyceridesecretions AT kowillemsvandijk caspase1deficiencyinmicereducesintestinaltriglycerideabsorptionandhepatictriglyceridesecretions AT patrickcnrensen caspase1deficiencyinmicereducesintestinaltriglycerideabsorptionandhepatictriglyceridesecretions |
| _version_ |
1721504022228107264 |
| spelling |
doaj-6e780bacf3b342febeb95866706387ee2021-04-28T06:07:33ZengElsevierJournal of Lipid Research0022-22752013-02-01542448456Caspase-1 deficiency in mice reduces intestinal triglyceride absorption and hepatic triglyceride secretion[S]Janna A. van Diepen0Rinke Stienstra1Irene O. C.M. Vroegrijk2Sjoerd A.A. van den Berg3Daniela Salvatori4Guido J. Hooiveld5Sander Kersten6Cees J. Tack7Mihai G. Netea8Johannes W.A. Smit9Leo A.B. Joosten10Louis M. Havekes11Ko Willems van Dijk12Patrick C.N. Rensen13Department of General Internal Medicine, Endocrinology and Metabolic Diseases, Leiden University Medical Center, Leiden, The Netherlands; Department of Medicine, Radboud University Nijmegen Medical Centre, and Nijmegen Institute for Infection, Inflammation and Immunity (N4i), Nijmegen, The NetherlandsDepartment of Medicine, Radboud University Nijmegen Medical Centre, and Nijmegen Institute for Infection, Inflammation and Immunity (N4i), Nijmegen, The Netherlands; Nutrition, Metabolism, and Genomics group, Division of Human Nutrition, Wageningen University, Wageningen, The Netherlands; andDepartment of General Internal Medicine, Endocrinology and Metabolic Diseases, Leiden University Medical Center, Leiden, The NetherlandsDepartment of Human Genetics, Leiden University Medical Center, Leiden, The NetherlandsDepartment of Anatomy and Embryology, Leiden University Medical Center, Leiden, The NetherlandsNutrition, Metabolism, and Genomics group, Division of Human Nutrition, Wageningen University, Wageningen, The Netherlands; andNutrition, Metabolism, and Genomics group, Division of Human Nutrition, Wageningen University, Wageningen, The Netherlands; andDepartment of Medicine, Radboud University Nijmegen Medical Centre, and Nijmegen Institute for Infection, Inflammation and Immunity (N4i), Nijmegen, The NetherlandsDepartment of Medicine, Radboud University Nijmegen Medical Centre, and Nijmegen Institute for Infection, Inflammation and Immunity (N4i), Nijmegen, The NetherlandsDepartment of General Internal Medicine, Endocrinology and Metabolic Diseases, Leiden University Medical Center, Leiden, The Netherlands; Department of Medicine, Radboud University Nijmegen Medical Centre, and Nijmegen Institute for Infection, Inflammation and Immunity (N4i), Nijmegen, The NetherlandsDepartment of Medicine, Radboud University Nijmegen Medical Centre, and Nijmegen Institute for Infection, Inflammation and Immunity (N4i), Nijmegen, The NetherlandsDepartment of General Internal Medicine, Endocrinology and Metabolic Diseases, Leiden University Medical Center, Leiden, The Netherlands; Department of Cardiology, Leiden University Medical Center, Leiden, The Netherlands; Netherlands Organization for Applied Scientific Research–Biosciences, Gaubius Laboratory, Leiden, The Netherlands.Department of General Internal Medicine, Endocrinology and Metabolic Diseases, Leiden University Medical Center, Leiden, The Netherlands; Department of Human Genetics, Leiden University Medical Center, Leiden, The NetherlandsTo whom correspondence should be addressed P.C.N.Rensen@lumc.nl; Department of General Internal Medicine, Endocrinology and Metabolic Diseases, Leiden University Medical Center, Leiden, The Netherlands; To whom correspondence should be addressed P.C.N.Rensen@lumc.nlCaspase-1 is known to activate the proinflammatory cytokines IL-1β and IL-18. Additionally, it can cleave other substrates, including proteins involved in metabolism. Recently, we showed that caspase-1 deficiency in mice strongly reduces high-fat diet-induced weight gain, at least partly caused by an increased energy production. Increased feces secretion by caspase-1-deficient mice suggests that lipid malabsorption possibly further reduces adipose tissue mass. In this study we investigated whether caspase-1 plays a role in triglyceride-(TG)-rich lipoprotein metabolism using caspase-1-deficient and wild-type mice. Caspase-1 deficiency reduced the postprandial TG response to an oral lipid load, whereas TG-derived fatty acid (FA) uptake by peripheral tissues was not affected, demonstrated by unaltered kinetics of [3H]TG-labeled very low-density lipoprotein (VLDL)-like emulsion particles. An oral gavage of [3H]TG-containing olive oil revealed that caspase-1 deficiency reduced TG absorption and subsequent uptake of TG-derived FA in liver, muscle, and adipose tissue. Similarly, despite an elevated hepatic TG content, caspase-1 deficiency reduced hepatic VLDL-TG production. Intestinal and hepatic gene expression analysis revealed that caspase-1 deficiency did not affect FA oxidation or FA uptake but rather reduced intracellular FA transport, thereby limiting lipid availability for the assembly and secretion of TG-rich lipoproteins. The current study reveals a novel function for caspase-1, or caspase-1-cleaved substrates, in controlling intestinal TG absorption and hepatic TG secretion.http://www.sciencedirect.com/science/article/pii/S0022227520428093caspase-1chylomicronintestinelipid absorptionlivertriglyceride metabolism |