Vitamin D ameliorates adipose browning in chronic kidney disease cachexia

Abstract Patients with chronic kidney disease (CKD) are often 25(OH)D3 and 1,25(OH)2D3 insufficient. We studied whether vitamin D repletion could correct aberrant adipose tissue and muscle metabolism in a mouse model of CKD-associated cachexia. Intraperitoneal administration of 25(OH)D3 and 1,25(OH)...

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Autores principales:	Wai W. Cheung, Wei Ding, Hal M. Hoffman, Zhen Wang, Sheng Hao, Ronghao Zheng, Alex Gonzalez, Jian-Ying Zhan, Ping Zhou, Shiping Li, Mary C. Esparza, Richard L. Lieber, Robert H. Mak
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2020
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/c7f89d5c634042d6a54496a2da92b2bc
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spelling	oai:doaj.org-article:c7f89d5c634042d6a54496a2da92b2bc2021-12-02T19:02:37ZVitamin D ameliorates adipose browning in chronic kidney disease cachexia10.1038/s41598-020-70190-z2045-2322https://doaj.org/article/c7f89d5c634042d6a54496a2da92b2bc2020-08-01T00:00:00Zhttps://doi.org/10.1038/s41598-020-70190-zhttps://doaj.org/toc/2045-2322Abstract Patients with chronic kidney disease (CKD) are often 25(OH)D3 and 1,25(OH)2D3 insufficient. We studied whether vitamin D repletion could correct aberrant adipose tissue and muscle metabolism in a mouse model of CKD-associated cachexia. Intraperitoneal administration of 25(OH)D3 and 1,25(OH)2D3 (75 μg/kg/day and 60 ng/kg/day respectively for 6 weeks) normalized serum concentrations of 25(OH)D3 and 1,25(OH)2D3 in CKD mice. Vitamin D repletion stimulated appetite, normalized weight gain, and improved fat and lean mass content in CKD mice. Vitamin D supplementation attenuated expression of key molecules involved in adipose tissue browning and ameliorated expression of thermogenic genes in adipose tissue and skeletal muscle in CKD mice. Furthermore, repletion of vitamin D improved skeletal muscle fiber size and in vivo muscle function, normalized muscle collagen content and attenuated muscle fat infiltration as well as pathogenetic molecular pathways related to muscle mass regulation in CKD mice. RNAseq analysis was performed on the gastrocnemius muscle. Ingenuity Pathway Analysis revealed that the top 12 differentially expressed genes in CKD were correlated with impaired muscle and neuron regeneration, enhanced muscle thermogenesis and fibrosis. Importantly, vitamin D repletion normalized the expression of those 12 genes in CKD mice. Vitamin D repletion may be an effective therapeutic strategy for adipose tissue browning and muscle wasting in CKD patients.Wai W. CheungWei DingHal M. HoffmanZhen WangSheng HaoRonghao ZhengAlex GonzalezJian-Ying ZhanPing ZhouShiping LiMary C. EsparzaRichard L. LieberRobert H. MakNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 10, Iss 1, Pp 1-15 (2020)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Wai W. Cheung Wei Ding Hal M. Hoffman Zhen Wang Sheng Hao Ronghao Zheng Alex Gonzalez Jian-Ying Zhan Ping Zhou Shiping Li Mary C. Esparza Richard L. Lieber Robert H. Mak Vitamin D ameliorates adipose browning in chronic kidney disease cachexia
description	Abstract Patients with chronic kidney disease (CKD) are often 25(OH)D3 and 1,25(OH)2D3 insufficient. We studied whether vitamin D repletion could correct aberrant adipose tissue and muscle metabolism in a mouse model of CKD-associated cachexia. Intraperitoneal administration of 25(OH)D3 and 1,25(OH)2D3 (75 μg/kg/day and 60 ng/kg/day respectively for 6 weeks) normalized serum concentrations of 25(OH)D3 and 1,25(OH)2D3 in CKD mice. Vitamin D repletion stimulated appetite, normalized weight gain, and improved fat and lean mass content in CKD mice. Vitamin D supplementation attenuated expression of key molecules involved in adipose tissue browning and ameliorated expression of thermogenic genes in adipose tissue and skeletal muscle in CKD mice. Furthermore, repletion of vitamin D improved skeletal muscle fiber size and in vivo muscle function, normalized muscle collagen content and attenuated muscle fat infiltration as well as pathogenetic molecular pathways related to muscle mass regulation in CKD mice. RNAseq analysis was performed on the gastrocnemius muscle. Ingenuity Pathway Analysis revealed that the top 12 differentially expressed genes in CKD were correlated with impaired muscle and neuron regeneration, enhanced muscle thermogenesis and fibrosis. Importantly, vitamin D repletion normalized the expression of those 12 genes in CKD mice. Vitamin D repletion may be an effective therapeutic strategy for adipose tissue browning and muscle wasting in CKD patients.
format	article
author	Wai W. Cheung Wei Ding Hal M. Hoffman Zhen Wang Sheng Hao Ronghao Zheng Alex Gonzalez Jian-Ying Zhan Ping Zhou Shiping Li Mary C. Esparza Richard L. Lieber Robert H. Mak
author_facet	Wai W. Cheung Wei Ding Hal M. Hoffman Zhen Wang Sheng Hao Ronghao Zheng Alex Gonzalez Jian-Ying Zhan Ping Zhou Shiping Li Mary C. Esparza Richard L. Lieber Robert H. Mak
author_sort	Wai W. Cheung
title	Vitamin D ameliorates adipose browning in chronic kidney disease cachexia
title_short	Vitamin D ameliorates adipose browning in chronic kidney disease cachexia
title_full	Vitamin D ameliorates adipose browning in chronic kidney disease cachexia
title_fullStr	Vitamin D ameliorates adipose browning in chronic kidney disease cachexia
title_full_unstemmed	Vitamin D ameliorates adipose browning in chronic kidney disease cachexia
title_sort	vitamin d ameliorates adipose browning in chronic kidney disease cachexia
publisher	Nature Portfolio
publishDate	2020
url	https://doaj.org/article/c7f89d5c634042d6a54496a2da92b2bc
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Vitamin D ameliorates adipose browning in chronic kidney disease cachexia

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