Vitamin D ameliorates adipose browning in chronic kidney disease cachexia

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*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

23 Scopus citations

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.

Original languageEnglish (US)
Article number14175
JournalScientific reports
Volume10
Issue number1
DOIs
StatePublished - Dec 1 2020

Funding

We thank Dr. Jianhua Shao, UCSD Pediatric Diabetes Research Center for the use of EchoMRI-100™. The authors thank James A. Proudfoot for his assistance in statistical analysis. This project was partially supported by the National Institutes of Health (NIH), UL1TR001442 of CTSA funding. This project was funded by National Institutes of Health Grant R01 DK125811 to RHM and U01DK03012 to RLL and RHM, Shanghai Pujiang Program 17PJD021 and distinguished Young Scholar of Ninth People’s Hospital jyyq09201701 (W D), Nature Scientific Foundation of Heilongjiang Province (LC2017034) and Research fund for Young and Middle-aged Innovative Science of the Second Affiliated Hospital of Harbin Medical University (CX2016-03) (P Z), Yangzhou University Overseas Study Program (S L) and National Institutes of Health R24-HD050837 (R L L). This work was also supported in part by Research Career Scientist Award Number IK6 RX003351 from the United States (U.S.) Department of Veterans Affairs Rehabilitation R&D (Rehab RD) Service.

ASJC Scopus subject areas

  • General

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