Cytarabine induces cachexia with lipid malabsorption via zippering the junctions of lacteal in murine small intestine
Chemotherapy-induced cachexia causes severe metabolic abnormalities independently of cancer and reduces the therapeutic efficacy of chemotherapy. The underlying mechanism of chemotherapy-induced cachexia remains unclear. Here we investigated the cytarabine (CYT)-induced alteration in energy balance...
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| Format: | Article |
| Language: | English |
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Elsevier
2023-06-01
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| Series: | Journal of Lipid Research |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S0022227523000603 |
| _version_ | 1827918554257686528 |
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| author | Mi-Rae Park Hye-Jin Lee Hye-Min Jang Nam Hoon Kim Jun-Seok Lee Yong Taek Jeong Inho Kim Sang-Hyun Choi Kwan Sik Seo Dong-Hoon Kim |
| author_facet | Mi-Rae Park Hye-Jin Lee Hye-Min Jang Nam Hoon Kim Jun-Seok Lee Yong Taek Jeong Inho Kim Sang-Hyun Choi Kwan Sik Seo Dong-Hoon Kim |
| author_sort | Mi-Rae Park |
| collection | DOAJ |
| description | Chemotherapy-induced cachexia causes severe metabolic abnormalities independently of cancer and reduces the therapeutic efficacy of chemotherapy. The underlying mechanism of chemotherapy-induced cachexia remains unclear. Here we investigated the cytarabine (CYT)-induced alteration in energy balance and its underlying mechanisms in mice. We compared energy balance-associated parameters among the three groups of mice: CON, CYT, and PF (pair-fed mice with the CYT group) that were intravenously administered vehicle or CYT. Weight gain, fat mass, skeletal muscle mass, grip strength, and nocturnal energy expenditure were significantly lowered in the CYT group than in the CON and PF groups. The CYT group demonstrated less energy intake than the CON group and higher respiratory quotient than the PF group, indicating that CYT induced cachexia independently from the anorexia-induced weight loss. Serum triglyceride was significantly lower in the CYT group than in the CON group, whereas the intestinal mucosal triglyceride levels and the lipid content within the small intestine enterocyte were higher after lipid loading in the CYT group than in the CON and PF groups, suggesting that CYT inhibited lipid uptake in the intestine. This was not associated with obvious intestinal damage. The CYT group showed increased zipper-like junctions of lymphatic endothelial vessel in duodenal villi compared to that in the CON and CYT groups, suggesting their imperative role in the CYT-induced inhibition of lipid uptake. CYT worsens cachexia independently of anorexia by inhibiting the intestinal lipid uptake, via the increased zipper-like junctions of lymphatic endothelial vessel. |
| first_indexed | 2024-03-13T03:44:14Z |
| format | Article |
| id | doaj.art-1683d5e8d8884c39a941c7f03da1a069 |
| institution | Directory Open Access Journal |
| issn | 0022-2275 |
| language | English |
| last_indexed | 2024-03-13T03:44:14Z |
| publishDate | 2023-06-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Journal of Lipid Research |
| spelling | doaj.art-1683d5e8d8884c39a941c7f03da1a0692023-06-23T04:42:17ZengElsevierJournal of Lipid Research0022-22752023-06-01646100387Cytarabine induces cachexia with lipid malabsorption via zippering the junctions of lacteal in murine small intestineMi-Rae Park0Hye-Jin Lee1Hye-Min Jang2Nam Hoon Kim3Jun-Seok Lee4Yong Taek Jeong5Inho Kim6Sang-Hyun Choi7Kwan Sik Seo8Dong-Hoon Kim9Department of Pharmacology, Korea University College of Medicine, Seoul, Republic of Korea; Department of Biomedical Sciences, Korea University College of Medicine, Seoul, Republic of KoreaDepartment of Pharmacology, Korea University College of Medicine, Seoul, Republic of KoreaDepartment of Pharmacology, Korea University College of Medicine, Seoul, Republic of KoreaDivision of Endocrinology and Metabolism, Department of Internal Medicine, Korea University College of Medicine, Seoul, Republic of KoreaDepartment of Pharmacology, Korea University College of Medicine, Seoul, Republic of KoreaDepartment of Pharmacology, Korea University College of Medicine, Seoul, Republic of Korea; Department of Biomedical Sciences, Korea University College of Medicine, Seoul, Republic of KoreaDepartment of Internal Medicine, Seoul National University College of Medicine, Seoul National University Hospital, Seoul, Republic of KoreaDepartment of Pharmacology, Korea University College of Medicine, Seoul, Republic of KoreaDepartment of Rehabilitation Medicine, Seoul National University Hospital, Seoul, Republic of Korea; For correspondence: Dong-Hoon Kim; Kwan Sik SeoDepartment of Pharmacology, Korea University College of Medicine, Seoul, Republic of Korea; Department of Biomedical Sciences, Korea University College of Medicine, Seoul, Republic of Korea; For correspondence: Dong-Hoon Kim; Kwan Sik SeoChemotherapy-induced cachexia causes severe metabolic abnormalities independently of cancer and reduces the therapeutic efficacy of chemotherapy. The underlying mechanism of chemotherapy-induced cachexia remains unclear. Here we investigated the cytarabine (CYT)-induced alteration in energy balance and its underlying mechanisms in mice. We compared energy balance-associated parameters among the three groups of mice: CON, CYT, and PF (pair-fed mice with the CYT group) that were intravenously administered vehicle or CYT. Weight gain, fat mass, skeletal muscle mass, grip strength, and nocturnal energy expenditure were significantly lowered in the CYT group than in the CON and PF groups. The CYT group demonstrated less energy intake than the CON group and higher respiratory quotient than the PF group, indicating that CYT induced cachexia independently from the anorexia-induced weight loss. Serum triglyceride was significantly lower in the CYT group than in the CON group, whereas the intestinal mucosal triglyceride levels and the lipid content within the small intestine enterocyte were higher after lipid loading in the CYT group than in the CON and PF groups, suggesting that CYT inhibited lipid uptake in the intestine. This was not associated with obvious intestinal damage. The CYT group showed increased zipper-like junctions of lymphatic endothelial vessel in duodenal villi compared to that in the CON and CYT groups, suggesting their imperative role in the CYT-induced inhibition of lipid uptake. CYT worsens cachexia independently of anorexia by inhibiting the intestinal lipid uptake, via the increased zipper-like junctions of lymphatic endothelial vessel.http://www.sciencedirect.com/science/article/pii/S0022227523000603cytarabinetriglyceridesmetabolic dysfunctioncachexiamalabsorptionsmall intestine |
| spellingShingle | Mi-Rae Park Hye-Jin Lee Hye-Min Jang Nam Hoon Kim Jun-Seok Lee Yong Taek Jeong Inho Kim Sang-Hyun Choi Kwan Sik Seo Dong-Hoon Kim Cytarabine induces cachexia with lipid malabsorption via zippering the junctions of lacteal in murine small intestine Journal of Lipid Research cytarabine triglycerides metabolic dysfunction cachexia malabsorption small intestine |
| title | Cytarabine induces cachexia with lipid malabsorption via zippering the junctions of lacteal in murine small intestine |
| title_full | Cytarabine induces cachexia with lipid malabsorption via zippering the junctions of lacteal in murine small intestine |
| title_fullStr | Cytarabine induces cachexia with lipid malabsorption via zippering the junctions of lacteal in murine small intestine |
| title_full_unstemmed | Cytarabine induces cachexia with lipid malabsorption via zippering the junctions of lacteal in murine small intestine |
| title_short | Cytarabine induces cachexia with lipid malabsorption via zippering the junctions of lacteal in murine small intestine |
| title_sort | cytarabine induces cachexia with lipid malabsorption via zippering the junctions of lacteal in murine small intestine |
| topic | cytarabine triglycerides metabolic dysfunction cachexia malabsorption small intestine |
| url | http://www.sciencedirect.com/science/article/pii/S0022227523000603 |
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