Deficiency in hormone-sensitive lipase accelerates the development of pancreatic cancer in conditional KrasG12D mice
Abstract Background Hormone sensitive lipase (HSL) is a neutral lipase that preferentially catalyzes the hydrolysis of diacylglycerol contributing to triacylglycerol breakdown in the adipose tissue. HSL has been implicated to play a role in tumor cachexia, a debilitating syndrome characterized by pr...
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| Format: | Article |
| Language: | English |
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BMC
2018-08-01
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| Series: | BMC Cancer |
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| Online Access: | http://link.springer.com/article/10.1186/s12885-018-4713-y |
| _version_ | 1818197781626486784 |
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| author | Mu Xu Hui-Hua Chang Xiaoman Jung Aune Moro Caroline Ei Ne Chou Jonathan King O. Joe Hines James Sinnett-Smith Enrique Rozengurt Guido Eibl |
| author_facet | Mu Xu Hui-Hua Chang Xiaoman Jung Aune Moro Caroline Ei Ne Chou Jonathan King O. Joe Hines James Sinnett-Smith Enrique Rozengurt Guido Eibl |
| author_sort | Mu Xu |
| collection | DOAJ |
| description | Abstract Background Hormone sensitive lipase (HSL) is a neutral lipase that preferentially catalyzes the hydrolysis of diacylglycerol contributing to triacylglycerol breakdown in the adipose tissue. HSL has been implicated to play a role in tumor cachexia, a debilitating syndrome characterized by progressive loss of adipose tissue. Consequently, pharmacological inhibitors of HSL have been proposed for the treatment of cancer-associated cachexia. In the present study we used the conditional KrasG12D (KC) mouse model of pancreatic ductal adenocarcinoma (PDAC) with a deficiency in HSL to determine the impact of HSL suppression on the development of PDAC. Methods KC;Hsl +/+ and KC;Hsl −/− mice were fed standard rodent chow for 20 weeks. At sacrifice, the incidence of PDAC was determined and inflammation in the mesenteric adipose tissue and pancreas was assessed histologically and by immunofluorescence. To determine statistical significance, ANOVA and two-tailed Student’s t-tests were performed. To compare PDAC incidence, a two-sided Fisher’s exact test was used. Results Compared to KC;Hsl +/+ mice, KC;Hsl −/− mice gained similar weight and displayed adipose tissue and pancreatic inflammation. In addition, KC;Hsl −/− mice had reduced levels of plasma insulin and leptin. Importantly, the increased adipose tissue and pancreatic inflammation was associated with a significant increase in PDAC incidence in KC;Hsl −/− mice. Conclusions HSL deficiency is associated with adipose tissue and pancreatic inflammation and accelerates PDAC development in the KC mouse model. |
| first_indexed | 2024-12-12T01:55:26Z |
| format | Article |
| id | doaj.art-07afe0ee8ea74324a7e7d940b7b07fe2 |
| institution | Directory Open Access Journal |
| issn | 1471-2407 |
| language | English |
| last_indexed | 2024-12-12T01:55:26Z |
| publishDate | 2018-08-01 |
| publisher | BMC |
| record_format | Article |
| series | BMC Cancer |
| spelling | doaj.art-07afe0ee8ea74324a7e7d940b7b07fe22022-12-22T00:42:22ZengBMCBMC Cancer1471-24072018-08-011811910.1186/s12885-018-4713-yDeficiency in hormone-sensitive lipase accelerates the development of pancreatic cancer in conditional KrasG12D miceMu Xu0Hui-Hua Chang1Xiaoman Jung2Aune Moro3Caroline Ei Ne Chou4Jonathan King5O. Joe Hines6James Sinnett-Smith7Enrique Rozengurt8Guido Eibl9Departments of Surgery, David Geffen School of Medicine, University of California, Los AngelesDepartments of Surgery, David Geffen School of Medicine, University of California, Los AngelesDepartments of Surgery, David Geffen School of Medicine, University of California, Los AngelesDepartments of Surgery, David Geffen School of Medicine, University of California, Los AngelesDepartments of Surgery, David Geffen School of Medicine, University of California, Los AngelesDepartments of Surgery, David Geffen School of Medicine, University of California, Los AngelesDepartments of Surgery, David Geffen School of Medicine, University of California, Los AngelesDepartments of Medicine, David Geffen School of Medicine, University of California, Los AngelesDepartments of Medicine, David Geffen School of Medicine, University of California, Los AngelesDepartments of Surgery, David Geffen School of Medicine, University of California, Los AngelesAbstract Background Hormone sensitive lipase (HSL) is a neutral lipase that preferentially catalyzes the hydrolysis of diacylglycerol contributing to triacylglycerol breakdown in the adipose tissue. HSL has been implicated to play a role in tumor cachexia, a debilitating syndrome characterized by progressive loss of adipose tissue. Consequently, pharmacological inhibitors of HSL have been proposed for the treatment of cancer-associated cachexia. In the present study we used the conditional KrasG12D (KC) mouse model of pancreatic ductal adenocarcinoma (PDAC) with a deficiency in HSL to determine the impact of HSL suppression on the development of PDAC. Methods KC;Hsl +/+ and KC;Hsl −/− mice were fed standard rodent chow for 20 weeks. At sacrifice, the incidence of PDAC was determined and inflammation in the mesenteric adipose tissue and pancreas was assessed histologically and by immunofluorescence. To determine statistical significance, ANOVA and two-tailed Student’s t-tests were performed. To compare PDAC incidence, a two-sided Fisher’s exact test was used. Results Compared to KC;Hsl +/+ mice, KC;Hsl −/− mice gained similar weight and displayed adipose tissue and pancreatic inflammation. In addition, KC;Hsl −/− mice had reduced levels of plasma insulin and leptin. Importantly, the increased adipose tissue and pancreatic inflammation was associated with a significant increase in PDAC incidence in KC;Hsl −/− mice. Conclusions HSL deficiency is associated with adipose tissue and pancreatic inflammation and accelerates PDAC development in the KC mouse model.http://link.springer.com/article/10.1186/s12885-018-4713-yPancreatic cancerHormone sensitive lipaseAdipose tissue inflammationPancreatic inflammationAnimal model |
| spellingShingle | Mu Xu Hui-Hua Chang Xiaoman Jung Aune Moro Caroline Ei Ne Chou Jonathan King O. Joe Hines James Sinnett-Smith Enrique Rozengurt Guido Eibl Deficiency in hormone-sensitive lipase accelerates the development of pancreatic cancer in conditional KrasG12D mice BMC Cancer Pancreatic cancer Hormone sensitive lipase Adipose tissue inflammation Pancreatic inflammation Animal model |
| title | Deficiency in hormone-sensitive lipase accelerates the development of pancreatic cancer in conditional KrasG12D mice |
| title_full | Deficiency in hormone-sensitive lipase accelerates the development of pancreatic cancer in conditional KrasG12D mice |
| title_fullStr | Deficiency in hormone-sensitive lipase accelerates the development of pancreatic cancer in conditional KrasG12D mice |
| title_full_unstemmed | Deficiency in hormone-sensitive lipase accelerates the development of pancreatic cancer in conditional KrasG12D mice |
| title_short | Deficiency in hormone-sensitive lipase accelerates the development of pancreatic cancer in conditional KrasG12D mice |
| title_sort | deficiency in hormone sensitive lipase accelerates the development of pancreatic cancer in conditional krasg12d mice |
| topic | Pancreatic cancer Hormone sensitive lipase Adipose tissue inflammation Pancreatic inflammation Animal model |
| url | http://link.springer.com/article/10.1186/s12885-018-4713-y |
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